2461-42-9|2-((Naphthalen-1-yloxy)methyl)oxirane| Ambeed

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Yield	Reaction Conditions	Operation in experiment
100%	for 1 h; Reflux	Reference Example 1 Synthesis of (RS)-naftopidil (HUHS1001) To a solution of 2-((1-naphthyloxy)methyl)oxirane (100 mg, 0.50 mmol) in ethanol (1 mL) was added 4-(2-methoxyphenyl)piperazine (95 μL, 0.60 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give (RS)-naftopidil (199 mg, 100percent). ¹H-NMR (400 MHz, CDCl₃) δ 2.72-2.76 (m, 4H), 2.92-2.95 (m, 2H), 3.09-3.18 (m, 4H), 3.87 (s, 3H), 4.16 (dd, J=9.6 and 5.0 Hz, 1H), 4.24 (dd, J=9.6 and 5.0 Hz, 1H), 4.28-4.34 (m, 1H), 6.84 (d, J=7.8 Hz, 1H), 6.87 (d, J=7.8 Hz, 1H), 6.91-6.98 (m, 2H), 7.00-7.04 (m, 1H), 7.39 (t, J=8.2 Hz, 1H), 7.44 (d, J=8.2 Hz, 1H), 7.47-7.51 (m, 2H), 7.79-7.81 (m, 1H), 8.26-8.29 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C₂₄H₂₉N₂O₃ ([M+H⁺]): 393.2173. Found 393.2148.
100%	at 20℃; for 1 h;	2-((1-naphthyloxy)methyl)4-(2-methoxyphenyl) piperazine (100 mg, 0.50 mmol) in ethanol (1 ml) solution of oxirane (95 μL, 0.60 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (RS)- (199 mg, 100percent) of crude product was purified by silica gel column chromatography to give naftopidil.

1
[ 90-15-3 ]
[ 106-89-8 ]
[ 2461-42-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium hydroxide; tetrabutylammomium bromide; potassium carbonate at 116℃; for 0.0333333h; Irradiation;
96%	With sodium hydroxide; tetrabutylammomium bromide; potassium carbonate at 116℃; for 0.0333333h; microwave irradiation;
95.4%	With sodium hydroxide In water at 65℃; for 5h;	1-1-1-2 Example 1-2 3-(1-naphthyloxy)-1,2-propylene oxide synthesis Weighing menadol (216.2g, 1.5mol, 1.0eq), polyethylene glycol 6000 (18.0g, 0.03mol, 0.02eq),Epichlorohydrin (347g, 3.75mol, 2.5eq) was added to a 2L four-necked flask, stirred and heated to 65°C to dissolve and clarify,Then dropwise add 30% NaOH aqueous solution (320g, 2.4mol, 1.6eq), dropwise for 1h,Then the temperature was controlled at 65 for 4h, the raw material disappeared by TLC monitoring (VPE/EA=5:1), the reaction was stopped, cooled to room temperature, the organic layer was separated and washed once with water, then the organic layer was concentrated under reduced pressure at 50 To dry,28. 6g of red-brown oily 3-(1-naphthyloxy)-1,2-propylene oxide was obtained with a molar yield of 95.4%.

93.2%	With sodium hydroxide; potassium iodide In ethanol at 30℃; for 0.2h; Microwave irradiation;	11.5 (5) Synthesis of 1-naphthyl epoxypropyl ether Into a 500mL three-necked round bottom flask, 10.03g 1-naphthol, 3.1g NaOH, 20.4g epichlorohydrin (S/R) and 0.5g KI were added, then 330mL ethanol was added. The flask was then placed in a microwave reactor. The reaction was performed at 30°C under stirring and 300W microwave irradiation for 12min. The reaction mixture was then removed and suction filtrated, and the filtrate was concentrated to obtain an oily substance. H2O was added to the oily substance, and the mixture was extracted with ethyl ether. The ethyl ether layers were combined and washed with a solution of NaOH, then washed with H2O once. The ether layer was dried using anhydrous magnesium sulfate and concentrated to obtain 12.95g of the product in a yield of 93.2%.
93.5%	With tetramethyl ammoniumhydroxide In acetonitrile for 5h; Reflux;	1.1; 2.1; 1.1; 2.1; 3.1; 4.1 Example 1 (1) According to the mass ratio of 2.0:1, add epichlorohydrin and naphthol to the acetonitrile solvent, stir and mix uniformly, then add 3.0% of the naphthol mass of tetramethylammonium hydroxide, and perform heating and refluxing reaction for 5h ; TLC detects the end of the reaction. After the reaction is completed, the cooling water is cooled to 45°C, and 15% sodium hydroxide solution is added dropwise. The amount of lye added is 1.5 times the mass of naphthol. After stirring, stand still to separate the lower alkaline water layer , The organic layer is washed with water until it is neutral. Collect the organic layer, recover epichlorohydrin, start stirring, heat to 90, vacuum ≤-0.08MPa, evaporate epichlorohydrin and solvent to obtain naphthyl glycidyl ether reaction liquid; yield of naphthyl glycidyl ether Is 93.5%;
90%	With potassium carbonate In acetone for 12h; Heating;
90%	With potassium carbonate In butanone for 12h; Heating;
89%	With sodium methylate In methanol	1 Example 1 Dissolve 100 g of 1-naphthol [1] in chloromethyloxylan [2],Sodium methoxide methanol solution was added dropwise. After completion of the reaction, the reaction was washed with water and the organic layer was concentrated to obtain 2-[(1-naphthyloxy) methyl] oxylan [3] (yield 89%).
88%	With KOH In methanol	1.1 Synthesis of 1-naphthyl glycidyl ether using 1-naphthol Example 1-(1) Synthesis of 1-naphthyl glycidyl ether using 1-naphthol 1-Naphthol (0.721 g, 5.0 mmol), as a starting material, was stirred with KOH (0.295 g, 5.0 mmol) and methanol (5 mL) in a 50 mL round-bottom flask. When the reagents were completely dissolved in the reaction solvent, the solvent was completely removed through evaporation and freeze-pump-thaw cycling. A dried potassium salt was obtained. After immersing the flask in an oil bath heated to 60 to 90° C., epichlorohydrin (3.91 mL, 10.0 mmol) was added both as a solvent and a reagent. After carrying out reaction at 60° C. for 30 minutes, the reaction solution was washed with brine. A product was extracted from the aqueous solution using a sufficient amount of CH2Cl2. After drying with Na2SO4, the solvent was removed under reduced pressure. The resulting crude product was purified by silica gel column chromatography (Rf=0.20, hexane:ethyl acetate=16:1, v/v). 1-Naphthyl glycidyl ether (0.881 g, 88%) was yielded. 1H NMR(CHCl3): δ 8.31 (m, 1H, H at ArH), 7.82 (m, 1H, H at ArH), 7.49 (m, 3H, Hs at ArH), 7.38 (m, 1H, H at ArH), 6.82 (m, 1H, H at ArH), 4.41 (m, 1H, H at C-3), 4.15 (m, 1H, H at C-3), 3.50 (m, 1H, H at C-2), 2.98 (m, 1H, H at C-1), 2.87 (m, 1H, H at C-1).
86%	With sodium hydroxide at 70 - 75℃; for 2h;
80%	With potassium carbonate In acetonitrile for 16h; Heating;
80%	With potassium carbonate In acetonitrile for 16h; Reflux; Inert atmosphere;
80%	With potassium carbonate In acetonitrile for 16h; Inert atmosphere; Reflux;
78%	Stage #1: α-naphthol With potassium hydroxide In dimethyl sulfoxide at 20℃; for 0.5h; Stage #2: epichlorohydrin In dimethyl sulfoxide for 16.5h;	3.a (a) Preparation of 2-((naphthalene-1-yloxy)methyl)oxirane (Compound 1) (a) Preparation of 2-((naphthalene-1-yloxy)methyl)oxirane (Compound 1) To a solution of 1-naphthol (3.0 g, 0.02 mol) in DMSO (10 mL), potassium hydroxy (flakes, 2.0 g, 0.06 mol) was added. The combined mixture was stirred at room temperature for 30 min and then epichlorohydrin (5.6 g, 4.7 mL, 0.06 mol) was added slowly over a period of 45 min and stirring was continued for 16 hours. The reaction was quenched with water (30 mL) and extracted with chloroform (250 mL). The combined organic layers were washed with 1N aqueous NaOH (250 mL), water (2100 mL) and brine (2100 mL) and dried over MgSO4. The solvent was removed under reduced pressure to provide Compound 1 as a yellow liquid (3.26 g, 78%). This product was used without further purification. The structure of Compound 1 is given below:
76%	Stage #1: α-naphthol With sodium hydride In N,N-dimethyl-formamide at 0 - 25℃; Inert atmosphere; Stage #2: epichlorohydrin In N,N-dimethyl-formamide at 25℃; for 12h;	5.1. General procedure for the synthesis of epoxide intermediates 8-11 General procedure: Sodium hydride (1.5 equiv) was added to a solution of the respective starting phenol (1 equiv) in DMF at 0 °C under nitrogen. The reaction mixture was raised to 25 °C and epichlorohydrin (5 equiv) was added dropwise over 2 min. The reactions were complete after 12 h as confirmed via TLC. The mixture was diluted with water (100 ml), extracted with EtOAc (3 × 100 ml) and dried over MgSO4. Excess epichlorohydrin and EtOAc was removed in vacuo to yield an oil which was purified by silica gel column chromatography.
76%	With potassium carbonate In acetonitrile at 70℃; for 9h;
76%	With sodium hydroxide In water at 60℃;	rac-α-Naphthyl glycidyl ether (1) was synthesized from α-naphthol and epichlorohydrin [20]. To a solution of α-naphthol (14.4 g, 100 mmol) in 25 mL epichlorohydrin (320 mmol), sodium hydroxide (200 mmol, 50% in water) was added very carefully at 60°C under mechanical stirring. After the starting material was consumed (as monitored by TLC), the mixture was extracted with ethyl acetate (3×50mL). The combined organic phase was washed with brine (3×30mL), dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (silica gel) using EtOAc/petroleum ether (1:10,v/v) as an eluent, affording epoxide 1 as light yellow oil. rac-α-Naphthyl glycidyl ether (1): yield, 76%; 1H NMR (400 MHz, CDCl3), δ/ppm: 8.28-8.30 (m, 1H), 7.76-7.78 (m, 1H), 7.43-7.47 (m, 3H), 7.33 (t, J=8.0 Hz, 1H), 6.75 (d, J=7.6 Hz, 1H), 4.32 (dd, J=2.8, 10.8 Hz, 1H), 4.06 (dd, J=5.6, 10.8, 1H), 3.42-3.43 (m, 1H), 2.89 (t, J=4.8 Hz, 1H), 2.78 (dd, J=2.4, 4.8 Hz, 1H).
72%	With cesium fluoride In N,N-dimethyl-formamide at 50℃; for 19.5h;
71%	With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃;
70%	With sodium hydroxide In water
69%	With sodium hydroxide In water for 0.0166667h; Irradiation;
67%	With sodium hydroxide
61%	Stage #1: α-naphthol With sodium hydride In N,N-dimethyl-formamide at 80℃; for 1h; Stage #2: epichlorohydrin In N,N-dimethyl-formamide at 80℃; for 4h; Further stages.;
61%	With potassium carbonate In acetone for 12h; Reflux;
57%	With sodium hydroxide In water at 82 - 85℃; for 11h;
54%	With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 24h; with maphthalene ring-<14C>-labeled educt;
34%	With sodium hydroxide In water at 20℃; for 5h;
18%	With potassium carbonate In acetone at 80℃; for 0.166667h; Microwave irradiation; Sealed tube;
11%	Stage #1: α-naphthol With sodium hydroxide In water; N,N-dimethyl-formamide at 20℃; for 0.833333h; Stage #2: epichlorohydrin In water; N,N-dimethyl-formamide at 20℃; for 120.67h;
	With alkali
	With sodium hydroxide 1.) 80 deg C, 2.) 4 h; Yield given. Multistep reaction;
	With Dowex resin (chloride form); sodium hydride 1.) reflux, 1 h, 2.) THF; Yield given. Multistep reaction;
	With sodium hydroxide 1.) 30 min, 2.) 40 deg C, 5 h; Multistep reaction;
	With sodium hydroxide In water
	With sodium hydride 1.) DMF, 80 deg C, 1 h, 2.) DMF, 140 deg C, 4 h; Yield given. Multistep reaction;
	With potassium carbonate In acetone Heating;
	With sodium methylate 1.) methanol, RT, 30 min, 2.) methanol, reflux, 8 h; Multistep reaction;
	With potassium <i>tert</i>-butylate 1.) DMF, 50 deg C, 30 min, 2.) DMF, 90 deg C, 3 h; Multistep reaction;
	With potassium carbonate In acetonitrile Heating;
46 % Chromat.	With sodium hydride In N,N-dimethyl-formamide at 50℃;
	With sodium hydroxide In ethanol
	With caustic In water at 90 - 95℃;
	With sodium hydroxide; tetrabutylammomium bromide; potassium carbonate Irradiation;
	With sodium hydroxide In water at 25 - 60℃;
	With NaH In <i>N</i>-methyl-acetamide; diethyl ether; mineral oil	5 EXAMPLE 5: EXAMPLE 5: Preparation of N-[2-Hydroxy-3-(1-naphthoxy)propyl]-1,1-dimethyl-2-(4-fluorophenyl) ethylamine Hydrochloride, Compound 2 STR5 A stirred suspension of sodium hydride (4.0 g of 60% NaH in mineral oil, 100 mmol) in dimethylformamide (DMF, 100 ml) was treated with 1-naphthol (14.42 g, 100 mmol). After stirring for 1 hour at ambient temperature (room temperature), the reaction was treated with epichlorohydrin (10.18 g, 110 mmol) and stirred for 1 hour at 100° C. The reaction was diluted with water and transferred to a separatory funnel using diethyl ether (500 ml). The organic phase was washed with 10% aqueous NaHCO3 (3*200 ml), dried over anhydrous sodium sulfate, filtered, and concentrated. Kugelrohr distillation (~100 microns) yielded 1-naphthyl glycidyl ether as a clear, colorless oil: GC/EI-MS, m/z (rel. int.) 200 (M+, 61), 184 (1), 169 (5), 157 (12), 144 (79), 129 (16), 115 (100), 101 (3), 89 (16).
	With potassium carbonate In acetone at 57℃; for 12h;	General procedure for synthesis of epoxides from phenols (1H NMR data not shown) A stirred solution of phenol (1 eq), potassium carbonate (2 eq) and epichlorohydrin (2 eq) in acetone was heated at reflux (57°C) for 12 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in vacuo. The resultant oil was taken up in toluene and washed successively with water, 1M sodium hydroxide and water. The organic phase was dried, filtered and concentrated in vacuo.
	With potassium carbonate In butanone Reflux;
	With sodium hydroxide In dimethyl sulfoxide at 40℃;
	Stage #1: α-naphthol With potassium hydroxide In ethanol; water at 20℃; for 0.5h; Stage #2: epichlorohydrin In ethanol; water at 20℃; for 8.5h;	Synthesis of Epoxide (Glycidyl-a-Naphthyl Ether (3)) We transfer 7.2 g (0.05 mol) of 1-naphthol and 5 g KOH toa round-bottom flask and added ethanol/H2O (9:1), afterwhich the mixture was stirred for 30 min at room temperature.After dissolution, 12 mL (0.15 mol) epichlorhydrinwas added dropwise slowly in 45 min and stirring was continuedat room temperature for 7 h. The reaction was leftunder magnetic stirring at room temperature for 45 min.TLC was carried out in an eluent system (hexane:ethyl acetate9:1) to monitor the end of the reaction. The reactionwas finished with H2O (50 mL) and extracted with chloroform(2 £ 75 mL). The combined organic layers werewashed with water (5 £ 100 mL) and sodium hydroxidesolution (2 £ 30 mL), and dried over sodium sulfate.Remove ethanol by vacuum evaporator and to give the glycidyl-a-naphthyl ether 3 in 96% yield. Extract aqueousphase with ethyl ether. The ethyl ether extract was driedwith anhydrous sodium sulfate. The next step was to filterand remove the solvent to obtain the crude brown oil.bp D 201-203C (lit[20] 203-205C]. 1H-NMR (400 MHz,CDCl3, d/ppm): 2.5-2.9 (m, 2H), 3.3 (m, 1H), 3.8-4.3 (m,2H) 6.4-6.8 (m. 1H), 6.9-7.7 (m,5H), 7.9-8.2 (m, 1H). 13CNMR(400 MHz, DMSO-d6, d/ppm): 154.2, 134.5, 134.7,127.7, 126.5, 126.1, 125.5, 123.6, 120.4, 107.4, 69.9, 49.8,22.4. IR (Neat, cm1): 3050, 2980, 1580, 1540, 1500, 1460,1390, 1340, 1310, 1270, 1240, 1180, 1100, 1080, 1020, 960,870, 790, 770, 750, 700, 670, 640, 570. Anal. Calcd. forC13H12O2: C 77.95, H 6.06%; Found C 77.90, H 5.97%;HRMS (EI) Calcd. for C13H12O2 [M]C, 200.1001, Found200.1008.
	With tetrabutyl-ammonium chloride; sodium hydroxide In water at 45℃; for 1h; Flow reactor;
	With potassium carbonate In acetone for 24h; Inert atmosphere; Reflux;	General method for synthesis of glycidyl ethers: General procedure: An oven dried 250 mL round bottom flask containing dry acetone (88 mL) was charged with target phenol (8.83 mmol, 1 equiv) and ground potassium carbonate (17.6 mmol, 2 equiv) under N2 and stirring. Epichlorohydrin (26.5 mmol, 3 equiv) was then ran in and the solution was heated under reflux for 24 h or until consumption of the phenol was visualized by TLC. Upon completion, the resulting solution was filtered and volatiles removed by rotary evaporation. The residue was loaded directly onto a silica gel column for purification.
	Stage #1: α-naphthol With sodium hydroxide In ethanol at 20℃; for 0.333333h; Stage #2: epichlorohydrin In ethanol at 20℃; for 24h;
90 %Chromat.	With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 70℃; for 0.333333h; Flow reactor;
	With potassium carbonate In acetone at 80℃; Sealed tube;	Typical procedure for the preparation of 1-13 General procedure: K2CO3 (4 mmol), epichlorohydrin (2 mmol), and the corresponding phenol (1 mmol) were mixed in a flask and then acetone (10 mL) was added as solvent. The suspension was reflux overnight at 80 °C. Then the mixture was filtrated with celite and the filtrate was concentrated under reduced pressure. The residue was purified by chromatograph on silica gel (petroleum ether/acetone = 100/1, v/v) to give compound 1-13. These products were consistent with the standard spectra reported in the literature [1].
	With potassium carbonate; potassium iodide
	Stage #1: α-naphthol With sodium hydroxide In water; dimethyl sulfoxide at 20℃; for 0.166667h; Stage #2: epichlorohydrin In water; dimethyl sulfoxide at 20℃; for 2.16h;	4.1.2. General procedure (A) for the synthesis of 2-(aryloxymethyl)oxiranes General procedure: Commercially unavailable 2-(aryloxymethyl)oxiranes were synthesized by following procedure as previously reported. To a solution of corresponding phenols in dimethyl sulfoxide (DMSO) at room temperature,NaOH aqueous solution (1 M, 1.2 equiv) was added, the volume ratio of solvent is DMSO:H2O = 2:1, the mixture was stirred for10 min and epichlorohydrin (1.5 equiv) was added dropwise within10 min, the reaction mixture was allowed to stirred for further 2 h.AcOEt was added to the mixture, which was washed by brine for 3times. The solvents were evaporated under vacuum, and the crude residuewas purified by column chromatography on silica gel.
	With potassium carbonate for 3h; Reflux;	2.2.1. General synthesis of 2-(aryloxymethyl)oxiranes (3a-f) General procedure: The general procedure for 3a-f synthesis was as follows. Into a doubled-necked round-bottomed flask (100 mL) phenol com- pounds ( 1a-f , shown in Scheme 1 ) (0.01 mol) and 20 mL of epichlorohydrin (EPH) ( 2 ) were added, and the mixture was re- fluxed for 180 min in the presence of a mild base (K 2 CO 3 ). Sub- sequently, the reaction mixture was cooled to ambient temper- ature and then the excess EPH was eliminated under vacuum. The achieved residue was poured into cold-water and mined with ethyl acetate. Finally, the obtained 2-(aryloxymethyl)oxiranes ( 3a-f ) product was dried in an oven under a vacuum.
	With potassium hydroxide In ethanol; water at 20℃; for 12h;	2.5. Synthesis of propranolol using catalyst 3 General procedure: In a 100 mL round bottom flask, 1-naphthol (1.2 g, 8.5 mmol) andKOH (0.5 g, mmol) were added to a mixture of ethanol/water (9:1) atroom temperature with stirring. After dissolution, chloropropyleneoxide (2.0 mL, 0.025 mol) was added drop wise and the reaction mixturestirred for 12 h. at room temperature. Volatiles were removed underreduced pressure. The aqueous phase was extracted with diethyl etherand dried with anhydrous sodium sulphate. The crude product as brownoil of 1-naphthyl glycidyl ether was obtained after removing the solventin 95% yield. For the synthesis of propranolol, the isolated 1-naphthylglycidyl ether (0.2 g, 1.0 mmol) and excess isopropylamine (4.0 mL,46.5 mmol) was added to a round-bottom flask having catalyst 3 (23 mg,8.58 wt%). The reaction mixture was allowed to refllux for 10 min andvolatiles were removed under reduced pressure to yield the desiredcrude product, purified by recrystallization in hexane. Yield: = 0.23 g(90%).

Reference： [1]Pchelka, Beata; Plenkiewicz, Jan [Organic Preparations and Procedures International, 1998, vol. 30, # 1, p. 87 - 90]
[2]Pchelka, Beata K.; Loupy, Andre; Petit, Alain [Tetrahedron, 2006, vol. 62, # 47, p. 10968 - 10979]
[3]Current Patent Assignee: CHANGZHOU TIANHUA PHARMACEUTICAL - CN111253267, 2020, A Location in patent: Paragraph 0026-0029
[4]Current Patent Assignee: NORTH-WEST UNIVERSITY (SOUTH AFRICA); NORTHWEST UNIVERSITY (CHINA) - EP2019090, 2009, A1 Location in patent: Page/Page column 11
[5]Current Patent Assignee: CHANGZHOU KANGPU PHARMACEUTICAL - CN113336656, 2021, A Location in patent: Paragraph 0014; 0019-0020; 0023-0024; 0027-0035; 0038-0040
[6]Kothakonda, Kiran Kumar; Bose, D. Subhas [Chemistry Letters, 2004, vol. 33, # 9, p. 1212 - 1213]
[7]Subhas Bose; Narsimha Reddy; Chavhan, Sanjay W. [Synthesis, 2005, # 14, p. 2345 - 2348]
[8]Current Patent Assignee: ASTENA HOLDINGS CO LTD - JP2021/104982, 2021, A Location in patent: Paragraph 0024-0025
[9]Current Patent Assignee: HANYANG UNIVERSITY - US2012/10315, 2012, A1
[10]Gella, I. M. [Pharmaceutical Chemistry Journal, 1986, vol. 20, # 6, p. 430 - 431][Khimiko-Farmatsevticheskii Zhurnal, 1986, vol. 20, # 6, p. 730 - 732]
[11]Shivani; Pujala, Brahmam; Chakraborti, Asit K. [Journal of Organic Chemistry, 2007, vol. 72, # 10, p. 3713 - 3722]
[12]Kumar, Amit; Parella, Ramarao; Babu, Srinivasarao Arulananda [Synlett, 2014, vol. 25, # 6, p. 835 - 842]
[13]Cabrera-Pardo, Jaime R.; Trowbridge, Aaron; Nappi, Manuel; Ozaki, Kyohei; Gaunt, Matthew J. [Angewandte Chemie - International Edition, 2017, vol. 56, # 39, p. 11958 - 11962][Angew. Chem., 2017, vol. 129, # 39, p. 12120 - 12124]
[14]Current Patent Assignee: ENZO BIOCHEM INC - US9250249, 2016, B2 Location in patent: Page/Page column 58
[15]Location in patent: experimental part Tacon, Claire; Guantai, Eric M.; Smith, Peter J.; Chibale, Kelly [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 2, p. 893 - 902]
[16]Seth, Kapileswar; Roy, Sudipta Raha; Pipaliya, Bhavin V.; Chakraborti, Asit K. [Chemical Communications, 2013, vol. 49, # 52, p. 5886 - 5888]
[17]Kong, Xu-Dong; Yu, Hui-Lei; Yang, Sheng; Zhou, Jiahai; Zeng, Bu-Bing; Xu, Jian-He [Journal of Molecular Catalysis B: Enzymatic, 2015, vol. 122, p. 275 - 281]
[18]Fagerstroem, Alexandra; Nilsson, Mikael; Berg, Ulf; Isaksson, Roland [Organic and Biomolecular Chemistry, 2006, vol. 4, # 16, p. 3067 - 3076]
[19]Kong, Xu-Dong; Ma, Qian; Zhou, Jiahai; Zeng, Bu-Bing; Xu, Jian-He [Angewandte Chemie - International Edition, 2014, vol. 53, # 26, p. 6641 - 6644][Angew. Chem., 2014, p. 6759 - 6762,4]
[20]Pitha; Milecki; Czajkowska; Kusiak [Journal of Medicinal Chemistry, 1983, vol. 26, # 1, p. 7 - 11]
[21]Khadilkar, Bhushan M.; Bendale, Pravin M. [Synthetic Communications, 1997, vol. 27, # 12, p. 2051 - 2056]
[22]Stankyavichene, L. M. M.; Puzanov, G. I.; Stankyavichyus, A. P.; Gendenshtein, E. I. [Pharmaceutical Chemistry Journal, 1983, vol. 17, # 5, p. 341 - 344][Khimiko-Farmatsevticheskii Zhurnal, 1983, vol. 17, # 5, p. 554 - 558]
[23]Kawamoto; Wills [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2001, # 16, p. 1916 - 1928]
[24]Location in patent: experimental part Samel, Amarish B.; Pai, Nandini R. [Journal of the Chinese Chemical Society, 2010, vol. 57, # 6, p. 1327 - 1330]
[25]Location in patent: experimental part Shapenova; Belyatskii; Panicheva [Russian Journal of Organic Chemistry, 2010, vol. 46, # 7, p. 1017 - 1020]
[26]Narimatsu, Shizuo; Arai, Takayuki; Watanabe, Toshiyuki; Masubuchi, Yasuhiro; Horie, Toshiharu; Suzuki, Tokuji; Ishikawa, Tsutomu; Tsutsui, Michio; Kumagai, Yoshito; Cho, Arthur K. [Chemical Research in Toxicology, 1997, vol. 10, # 3, p. 289 - 295]
[27]Location in patent: experimental part Zhao, Jing; Chu, Yan-Yan; Li, Ai-Tao; Ju, Xin; Kong, Xu-Dong; Pan, Jiang; Tang, Yun; Xu, Jian-He [Advanced Synthesis and Catalysis, 2011, vol. 353, # 9, p. 1510 - 1518]
[28]Schmitt, Martin L.; Hauser, Alexander-Thomas; Carlino, Luca; Pippel, Martin; Schulz-Fincke, Johannes; Metzger, Eric; Willmann, Dominica; Yiu, Teresa; Barton, Michelle; Schüle, Roland; Sippl, Wolfgang; Jung, Manfred [Journal of Medicinal Chemistry, 2013, vol. 56, # 18, p. 7334 - 7342]
[29]Faudone, Giuseppe; Bischoff-Kont, Iris; Rachor, Lea; Willems, Sabine; Zhubi, Rezart; Kaiser, Astrid; Chaikuad, Apirat; Knapp, Stefan; Fürst, Robert; Heering, Jan; Merk, Daniel [Journal of Medicinal Chemistry, 2021, vol. 64, # 12, p. 8727 - 8738]
[30]v. Lindemann [Chemische Berichte, 1891, vol. 24, p. 2149]
[31]Wang; Chen; Liu; Wong [Tetrahedron Letters, 1989, vol. 30, # 15, p. 1917 - 1920]
[32]Dishong, Dennis M.; Diamond, Craig J.; Cinoman, Michael I.; Gokel, Geoge W. [Journal of the American Chemical Society, 1983, vol. 105, # 3, p. 586 - 593]
[33]Oatis, J. E.; Baker, J. P.; McCarthy, J. R.; Knapp, D. R. [Journal of Medicinal Chemistry, 1983, vol. 26, # 12, p. 1687 - 1691]
[34]Glozman, O. M.; Ismailov, Sh. I.; Borisova, L. N.; Zhmurenko, L. A.; Orlova, E. K.; Zagorevskii, V. A. [Pharmaceutical Chemistry Journal, 1984, vol. 18, # 10, p. 687 - 692][Khimiko-Farmatsevticheskii Zhurnal, 1984, vol. 18, # 10, p. 1193 - 1198]
[35]Stankyavichene, L. M. M.; Raizhene, D. I. L.; Vizas, V. K.; Stankyavichyus, A. P.; Terent'ev, P. B. [Pharmaceutical Chemistry Journal, 1986, vol. 20, # 5, p. 323 - 328][Khimiko-Farmatsevticheskii Zhurnal, 1986, vol. 20, # 5, p. 548 - 553] Xiao, Zhihui; Yuan, Mu; Zhang, Si; Wu, Jun; Qi, Shuhua; Li, Qingxin [Magnetic Resonance in Chemistry, 2005, vol. 43, # 10, p. 869 - 872]
[36]Miyano, Sotaro; Lu, Linda D.-L.; Viti, Steven M.; Sharpless, K. Barry [Journal of Organic Chemistry, 1985, vol. 50, # 22, p. 4350 - 4360]
[37]Ohta, Hiromichi; Miyamae, Yoshitaka; Tsuchihashi, Gen-ichi [Agricultural and Biological Chemistry, 1989, vol. 53, # 1, p. 215 - 222]
[38]Sukuraba; Takahashi; Takeda; Achiwa [Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 5, p. 738 - 747]
[39]Suzuki, Tsuneji; Fukazawa, Nobuyuki; San-nohe, Kunio; Sato, Wakao; Yano, Osamu; Tsuruo, Takashi [Journal of Medicinal Chemistry, 1997, vol. 40, # 13, p. 2047 - 2052]
[40]Wright, Jon L.; Gregory, Tracy F.; Heffher, Thomas G.; MacKenzie, Robert G.; Pugsley, Thomas A.; Vander Meulen, Seth; Wise, Lawrence D. [Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 11, p. 1377 - 1380]
[41]Hori, Manabu; Janda, Kim D. [Journal of Organic Chemistry, 1998, vol. 63, # 3, p. 889 - 894]
[42]Perez; Pauwels; Pallard-Sigogneau; Fourrier; Chopin; Palmier; Colovray; Halazy [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 23, p. 3423 - 3428]
[43]Ozerov; Novikov; Brel' [Chemistry of Heterocyclic Compounds, 1999, vol. 35, # 1, p. 78 - 83]
[44]Pchelka, Beata Krystyna; Loupy, Andre; Plenkiewicz, Jan; Blanco, Luis [Tetrahedron Asymmetry, 2000, vol. 11, # 13, p. 2719 - 2732]
[45]Viswanathan; Chaudhari [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 19, p. 6581 - 6585]
[46]Current Patent Assignee: GLAXOSMITHKLINE PLC - US6022894, 2000, A
[47]Fullam, Elizabeth; Abuhammad, Areej; Wilson, David L.; Anderton, Matthew C.; Davies, Steve G.; Russell, Angela J.; Sim, Edith [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 4, p. 1185 - 1190]
[48]Location in patent: scheme or table Baker, Jillian G.; Adams, Luke A.; Salchow, Karolina; Mistry, Shailesh N.; Middleton, Richard J.; Hill, Stephen J.; Kellam, Barrie [Journal of Medicinal Chemistry, 2011, vol. 54, # 19, p. 6874 - 6887]
[49]Smith, Chris D.; Wang, Aixia; Vembaiyan, Kannan; Zhang, Jingqun; Xie, Cuihong; Zhou, Qiang; Wu, Guogen; Chen, S. R. Wayne; Back, Thomas G. [Journal of Medicinal Chemistry, 2013, vol. 56, # 21, p. 8626 - 8655]
[50]Gharib, Ali; Jahangir, Manouchehr; Roshani, Mina; Pesyan, Nader Noroozi; Scheeren; Mohadesazadeh, Sara; Lagzian, Shirin [Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 2015, vol. 45, # 3, p. 350 - 355]
[51]Nobuta, Tomoya; Xiao, Guozhi; Ghislieri, Diego; Gilmore, Kerry; Seeberger, Peter H. [Chemical Communications, 2015, vol. 51, # 82, p. 15133 - 15136]
[52]Lizza, Joseph R.; Moura-Letts, Gustavo [Synthesis, 2017, vol. 49, # 6, p. 1231 - 1242]
[53]Dong, Jun; Xu, Jiaxi [New Journal of Chemistry, 2018, vol. 42, # 11, p. 9037 - 9044]
[54]Morodo, Romain; Gérardy, Romaric; Petit, Guillaume; Monbaliu, Jean-Christophe M. [Green Chemistry, 2019, vol. 21, # 16, p. 4422 - 4433]
[55]Zhu, Ye-Fu; Wei, Bo-Le; Wang, Wen-Qiong; Xuan, Li-Jiang [Tetrahedron Letters, 2019, vol. 60, # 50]
[56]Fukuhara, Hiroshi; Gotoh, Akinobu; Kino, Yukari; Kurioka, Rina; Mabuchi, Miyuki; Matsunaga, Wataru; Nakao, Syuhei; Shimizu, Tadashi; Tanaka, Akito; Yamaguchi, Keiko; Yamamoto, Momoka [Bioorganic and medicinal chemistry letters, 2020, vol. 30, # 1]
[57]Chang, Qi; Long, Jing; Hu, Liqing; Chen, Zhuo; Li, Qianbin; Hu, Gaoyun [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 9]
[58]Sarojini, Perumal; Jeyachandran, Malaichamy; Sriram, Dharmarajan; Ranganathan, Palraj; Gandhimathi [Journal of Molecular Structure, 2021, vol. 1233]
[59]Chaudhary, Garima; Gupta, Neha; Singh, Amit Pratap [Polyhedron, 2021, vol. 207]

2
[ 2461-42-9 ]
[ 10576-12-2 ]
[ 67435-09-0 ]

Reference： [1]Patent: DE2651083,1978,
Chem.Abstr.,1978,vol. 89

3
[ 2461-42-9 ]
[ 1001-53-2 ]
N-{2-[2-Hydroxy-3-(naphthalen-1-yloxy)-propylamino]-ethyl}-acetamide [ No CAS ]

Reference： [1]Patent: CH605666,1978,
Patent: DE2458908,1975,
Chem.Abstr.,1976,vol. 84

4
[ 2461-42-9 ]
[ 62-53-3 ]
[ 21239-75-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With cerium(III) chloride heptahydrate; glycerol at 20℃; for 0.5h; regioselective reaction;
82%	With Selectfluor In neat (no solvent) at 70℃; for 0.166667h; Microwave irradiation;

Reference： [1]Location in patent: experimental part Narsaiah, A. Venkat; Wadavrao, Sachin B.; Reddy, A. Ramesh; Yadav [Synthesis, 2011, # 3, p. 485 - 489]
[2]Chauhan, Manmohan Singh; Yadav, Geeta Devi; Hussain, Firasat; Singh, Surendra [Catalysis science and technology, 2014, vol. 4, # 11, p. 3945 - 3952]
[3]Crowther,A.F.; Smith,L.H. [Journal of Medicinal Chemistry, 1968, vol. 11, # 5, p. 1009 - 1013]

5
[ 1011-17-2 ]
[ 2461-42-9 ]
[ 133347-36-1 ]

Yield	Reaction Conditions	Operation in experiment
43%	In ethanol at 20 - 70℃; for 3h;	Synthesis of 1-(4-(2-hydroxyphenyl) piperazin-1-yl)-3-(naphthalen-1-yloxy)propan-2-ol (8) To a solution of 2-((naphthalen-1-yloxy) methyl)oxirane (5) (100 mg, 0.50 mmol) in ethanol (1 mL), 4-(2-hydroxyphenyl)piperazine (95 μL, 0.60 mmol) was added at room temperature. After being stirred for 3 h at 70 C, the mixture was cooled and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (chloroform / methanol = 50 / 1) to give compound 8 (82 mg, 43%). IR (KBr, cm-1) 3331, 2999, 2856, 2781, 1579, 1211, 1182, 1139, 1106. 1H-NMR (400 MHz, CDCl3): δ 2.65-2.82 (m, 4H), 2.82-3.10 (m, 6H), 4.18 (dd, J = 9.2 and 4.6 Hz, 1H), 4.25 (dd, J = 9.2 and 5.0 Hz, 1H), 4.27-4.35 (m, 1H), 6.85 (d, J = 7.8 Hz, 1H), 6.87 (dd, J = 7.8 and 1.3 Hz, 1H), 6.96 (dd, J = 7.8 and 1.4 Hz, 1H), 7.09 (td, J = 7.8 and 1.4 Hz), 7.19 (dd, J = 7.8 and 1.4 Hz, 1H), 7.38 (t, J = 8.2 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.47-7.51 (m, 2H), 7.79-7.81 (m, 1H), 8.26-8.29 (m, 1H). 13C-NMR: (100 MHz, CDCl3) δ 52.61 (2C), 53.97 (2C), 60.87, 65.64, 70.33, 104.78, 114.07, 120.08, 120.62, 121.42, 121.82, 125.24, 125.50, 125.79, 126.45, 126.59, 127.50, 134.43, 138.71, 151.40, 154.28. ESI-HRMS (positive ion, sodium formate): calcd for C23H27N2O3+([M+H]+) 379.2022; found 379.2017.
	In isopropyl alcohol for 5h; Heating; Yield given;
	In isopropyl alcohol	1 1-(2-hydroxyphenyl)-4-[3-(naphth-1-yloxy)-2-hydroxypropyl]-piperazine EXAMPLE 1 1-(2-hydroxyphenyl)-4-[3-(naphth-1-yloxy)-2-hydroxypropyl]-piperazine 4.56 g. (0.025 mole) 1-(2-hydroxyphenyl)-piperazine and 5.6 g. (0.028 mole) 2,3-epoxypropyl naphthyl ether are dissolved in 50 ml. isopropanol and the solution obtained is heated under reflux for 5 hours, while stirring. Thereafter, the reaction mixture is diluted with a further 50 ml. isopropanol and acidified isopropanolic hydrochloric acid. A voluminous product precipitates out which is filtered off with suction, washed several times with isopropanol and recrystallized from methanol. Yield 8.8 g. (77% of theory); m.p. 249°-250° C.

Reference： [1]Fukuhara, Hiroshi; Gotoh, Akinobu; Kino, Yukari; Kurioka, Rina; Mabuchi, Miyuki; Matsunaga, Wataru; Nakao, Syuhei; Shimizu, Tadashi; Tanaka, Akito; Yamaguchi, Keiko; Yamamoto, Momoka [Bioorganic and medicinal chemistry letters, 2020, vol. 30, # 1]
[2]Kutscher; Engel; Fleischhauer; Niebch [Archiv der Pharmazie, 1993, vol. 326, # 10, p. 803 - 806]
[3]Current Patent Assignee: ROCHE HOLDING AG - US5037828, 1991, A

6
[ 2461-42-9 ]
[ 29772-54-1 ]
[ 127414-49-7 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1990,vol. 55,p. 1290 - 1296

7
[ 2461-42-9 ]
[ 102-97-6 ]
[ 2349-27-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	In ethanol at 70℃; for 18h;

Reference： [1]Miyano, Sotaro; Lu, Linda D.-L.; Viti, Steven M.; Sharpless, K. Barry [Journal of Organic Chemistry, 1985, vol. 50, # 22, p. 4350 - 4360]

8
[ 2461-42-9 ]
[ 75-31-0 ]
[ 525-66-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With acetic acid In water at 20℃; for 8h;	22-27 Preparation of compound 1-8 Add 3- (1-naphthyloxy) -1,2-epoxypropane (600 mg, 3 mmol), isopropylamine (887 mg, 15 mmol), water (5 mg, 0.30 mmol) and acetic acid (18 mg, 0.30 mmol) to In a reaction flask with a magnetic stirrer, the reaction was carried out at room temperature for 8 hours. The reaction was monitored by TLC, and the reaction solution was concentrated using a rotary evaporator to obtain colorless oily compound 1-8 (770 mg) with a yield of 99%.
96.3%	With Ni/Al₂O₃ at 50℃; for 3h;	1.2; 2.2; 1.2; 2.2; 3.2; 4.2 (2) Add Ni/α-Al2O3 (Ni loading is 4wt%) into the above reaction solution,Then add isopropylamine 1.5 times the mass of the reaction solution;The amount of catalyst added is 0.01% of the mass of isopropylamine,After the reaction is completed at 50°C for 3h, the reaction is completed, the normal pressure is slowly raised to 90°C to recover isopropylamine, the temperature is slowly lowered to normal temperature and then the temperature is cooled to below 10°C by freezing, crystallization is carried out for more than 12 hours, and the solid is precipitated. Dry at to get propranolol.The yield of propranolol was 96.3%;
94%	In water

93%	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane With calcium chloride In acetonitrile Stage #2: isopropylamine In acetonitrile Further stages.;
93%	In methanol at 50℃;	5.2. General procedure for synthesis of β-amino alcohols 12-14 General procedure: The respective amine (1.1 equiv) was added to 1 equiv of the respective epoxide in MeOH (1 ml per 0.06 mmol starting material). The mixture was stirred at 50 °C, for 12-24 h, until the reaction was complete (verified via TLC). The excess solvent was removed under reduced pressure and the resulting oil purified using either preparative TLC or column chromatography.
92%	at 20℃; for 1.5h;
92%	With Sulfated tungstate at 70℃; for 0.333333h; Green chemistry;	General procedure for epoxide opening reaction General procedure: Sulfated tungstate (10 wt%) was added to a solution of cyclohexene oxide (1 g, 10.18 mmol) and aniline (0.95 g, 10.18 mmol) in solvent-free condition and the mixture was stirred at room temperature. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with ethyl acetate (15 ml) and filtered to recover the catalyst. Organic layer washed with water (10 ml), dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by chromatography on silica gel (60-120) with hexane-ethyl acetate (8:2) as eluent to get pure 2-(phenylamino) cyclohexanol as a white solid.
92.6%	With N-ethyl-N,N-diisopropylamine In toluene at 20 - 35℃; for 6.5h;	2-1-2-2 Example 2-2 Synthesis of Propranolol Dissolve 3-(1-naphthyloxy)-1,2-propylene oxide (160g, 0.8mol, 1.0eq) and isopropylamine (108g, 1.2mol, 1.5eq) in 300mL toluene,Then, N,N-diisopropylethylamine (41.4g, 0.32mol, 0.4eq) was added dropwise at room temperature, added dropwise for 30min, and the temperature was raised to 35°C, and the reaction was incubated for 6h.TLC monitors the disappearance of raw materials (VCHCl3/MeOH=20:1), stop the reaction, cool to 5, precipitate solids, filter, and dry192.1 g of crude propranolol was obtained, the yield was 92.6%, and the HPLC purity was 99.3%.
90%	With cerium(III) chloride heptahydrate; glycerol at 20℃; for 0.5h; regioselective reaction;
85%	With iron oxide In neat (no solvent) at 20℃; for 20h; Green chemistry; regioselective reaction;	General procedure: Epoxide (1.5-2 mmol), amine(1.0 mmol) and nano Fe3O4 (10 mol%, 23 mg, particle size= <50 nm) were stirred at r.t. open to the atmosphere for20 h. EtOAc (1-2 mL) was then added and the mixture wasstirred for 1-2 min. A magnet was then externally applied tothe flask and the catalyst was allowed to accumulate at thewalls of the flask; the resulting clear solution was transferredto a fresh flask by using a pipette. This step was repeatedtwice more, and the combined organic layers were dried overanhydrous Na2SO4, filtered, and the solvent evaporated.Purification by column chromatography on silica gel(EtOAc-hexanes, 20:80) gave the pure products. (c) All thereactions were carried out at r.t (range 28-32 °C) unlessotherwise mentioned. (d) When one of the substrates(epoxide or amine) was a solid, to facilitate homogeneousstirring, the reaction was carried out by using 1 mmol of thesolid sample and the other corresponding liquid sample inexcess (2 mmol) and the yield was calculated based on thelimiting reagent.
84.1%	In toluene at 80℃; for 18h; with naphthalene ring-<14C>-labeled educt;
82%	In ethanol for 3h; Heating;
72%	With zinc(II) perchlorate hexahydrate at 20℃; for 1h;
67%	With silica gel for 0.5h; Irradiation;
	In propan-1-ol Heating;
	With lithium aluminium tetrahydride 1.) THF, 25 deg C, 15-30 min, 2.) 0 deg C, 4 h; Yield given. Multistep reaction;
	In water for 3h; Heating;
	In methanol for 3h; Heating; Yield given;
	at 60℃;
	In water Reflux;	Synthesis of (±)-Propranolol (4) We transferred 0.2 g (1.0 mmol) of the solution of glycidyla-naphthyl ether 3 (2.0 g, 10 mmol) in excess 20 mL isopropylamine(235 mmol; 2.78 g) and water (1 mL). Removal ofsolvent yielded crude ()-propranolol (2.38 g, 92%), whichcould be purified by recrystallization in hexane.Mp D 95C (lit.[19, 20] 96C), 1H-NMR (400 MHz, CDCl3,d/ppm): 1.2 (d, 6H), 2.4-3.1 (m, 4H), 6.8-8.3 (m, 7H). 13CNMR(400 MHz, DMSO-d6, d/ppm): 154.3, 134.6, 134.4,127.5, 126.6, 126.2,123.6, 70.8, 69.8, 49.6, 49.1, 23.8. IR(Neat, cm1): 3450, 3200, 3050, 2980, 1630, 1590, 1580,1500, 1460, 1400, 1340, 1320, 1270, 1240, 1180, 1160, 1100,1070, 1020, 960, 870, 790, 770, 760, 640, 620, 570, 520. Anal.Calcd. for C16H21NO2: C 74.11, H 8.15, N 5.41%;Found C 74.06, H 8.11, N 5.48%; HRMS (EI) Calcd. forC16H21NO2 [M]C, 259.2004, Found 259.2009;
	In ethanol; toluene at 120℃; for 0.333333h; Flow reactor;
75 %Chromat.	In dimethyl sulfoxide at 140℃; for 0.333333h; Flow reactor;
	In methanol at 45℃; for 48h;	1.05 g of compound 1a dissolved in 10mL of methanolwas added to 15mL of isopropylamine (12mM) and stirredat 45°C until obtaining the yellow-brown solution (48 h) andsolution was cooled to 5°C. en, 1.5 ml of HCl (2 M) wasdropped slowly into the resulting mixture, followed byadding NaOH (2 M) until white precipitate appeared. eprecipitate was washed by water, isolated by CC using amixture of H: E 5 : 5. Finally, 0.738 g of 1-(isopropylamino)-3-(naphthalen-1-yloxy) propan-2-ol (compound2) or propranolol was collected (Figure 2).
0.23 g	With Cu(II)-L-propylsilyl immobilized on mesoporous MCM-41 based solid Lewis acid catalyst for 0.166667h; Reflux;	2.5. Synthesis of propranolol using catalyst 3 General procedure: In a 100 mL round bottom flask, 1-naphthol (1.2 g, 8.5 mmol) andKOH (0.5 g, mmol) were added to a mixture of ethanol/water (9:1) atroom temperature with stirring. After dissolution, chloropropyleneoxide (2.0 mL, 0.025 mol) was added drop wise and the reaction mixturestirred for 12 h. at room temperature. Volatiles were removed underreduced pressure. The aqueous phase was extracted with diethyl etherand dried with anhydrous sodium sulphate. The crude product as brownoil of 1-naphthyl glycidyl ether was obtained after removing the solventin 95% yield. For the synthesis of propranolol, the isolated 1-naphthylglycidyl ether (0.2 g, 1.0 mmol) and excess isopropylamine (4.0 mL,46.5 mmol) was added to a round-bottom flask having catalyst 3 (23 mg,8.58 wt%). The reaction mixture was allowed to refllux for 10 min and volatiles were removed under reduced pressure to yield the desired crude product, purified by recrystallization in hexane. Yield: = 0.23 g(90%). Melting point: 94 C. 1H NMR (400 MHz, CDCl3), (ppm): 8.24(1H,d), 7.79 (1H, m), 7.47 (3H, m), 7.36 (1H, t), 6.82 (1H, d), 4.16 (3H,m) 2.96 (1H, dd), 2.86 (2H, m) and 1.1 (6H, m).13C NMR (100 MHz,CDCl3), (ppm): 154.5, 134.8, 127.64, 126.56, 125.91, 125.61, 125.37,125.30, 121.89, 120.68, 105.00, 70.79, 68.57, 49.64, 48.98 and 22.88.ESI-MS m/z calculated for C16H21NO2 is 259.34; found 260.17 [M +H+].

Reference： [1]Current Patent Assignee: YUNNAN UNIVERSITY - CN110885292, 2020, A Location in patent: Paragraph 0142-0160
[2]Current Patent Assignee: CHANGZHOU KANGPU PHARMACEUTICAL - CN113336656, 2021, A Location in patent: Paragraph 0015; 0019; 0021; 0023-0025; 0027-0034; 0036; ...
[3]Carlsen, Per H.; Aase, Kristin J. [Acta Chemica Scandinavica, 1993, vol. 47, # 6, p. 617 - 619]
[4]Kawamoto; Wills [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2001, # 16, p. 1916 - 1928]
[5]Location in patent: experimental part Tacon, Claire; Guantai, Eric M.; Smith, Peter J.; Chibale, Kelly [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 2, p. 893 - 902]
[6]Chakraborti, Asit K.; Kondaskar, Atul; Rudrawar, Santosh [Tetrahedron, 2004, vol. 60, # 41, p. 9085 - 9091]
[7]Pathare, Sagar P.; Akamanchi, Krishnacharya G. [Tetrahedron Letters, 2013, vol. 54, # 48, p. 6455 - 6459]
[8]Current Patent Assignee: CHANGZHOU TIANHUA PHARMACEUTICAL - CN111253267, 2020, A Location in patent: Paragraph 0030-0033
[9]Location in patent: experimental part Narsaiah, A. Venkat; Wadavrao, Sachin B.; Reddy, A. Ramesh; Yadav [Synthesis, 2011, # 3, p. 485 - 489]
[10]Kumar, Amit; Parella, Ramarao; Babu, Srinivasarao Arulananda [Synlett, 2014, vol. 25, # 6, p. 835 - 842]
[11]Narimatsu, Shizuo; Arai, Takayuki; Watanabe, Toshiyuki; Masubuchi, Yasuhiro; Horie, Toshiharu; Suzuki, Tokuji; Ishikawa, Tsutomu; Tsutsui, Michio; Kumagai, Yoshito; Cho, Arthur K. [Chemical Research in Toxicology, 1997, vol. 10, # 3, p. 289 - 295]
[12]Fagerstroem, Alexandra; Nilsson, Mikael; Berg, Ulf; Isaksson, Roland [Organic and Biomolecular Chemistry, 2006, vol. 4, # 16, p. 3067 - 3076]
[13]Shivani; Pujala, Brahmam; Chakraborti, Asit K. [Journal of Organic Chemistry, 2007, vol. 72, # 10, p. 3713 - 3722]
[14]Pchelka, Beata; Plenkiewicz, Jan [Organic Preparations and Procedures International, 1998, vol. 30, # 1, p. 87 - 90]
[15]Schulz [Pharmazie, 1968, vol. 23, # 5, p. 240 - 242]
[16]Solladie-Cavallo, A.; Bencheqroun, M. [Journal of Organic Chemistry, 1992, vol. 57, # 22, p. 5831 - 5834]
[17]Sukuraba; Takahashi; Takeda; Achiwa [Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 5, p. 738 - 747]
[18]Damle, Subhash V.; Patil, Prashant N.; Salunkhe, Manikrao M. [Synthetic Communications, 1999, vol. 29, # 10, p. 1639 - 1644]
[19]Location in patent: body text Pihlaja, Kalevi; Aaljoki, Kari; Lyytinen, Maija-Riitta; Huusko, Marja-Liisa; Hotokka, Marjut [ARKIVOC, 2011, vol. 2011, # 5, p. 188 - 199]
[20]Gharib, Ali; Jahangir, Manouchehr; Roshani, Mina; Pesyan, Nader Noroozi; Scheeren; Mohadesazadeh, Sara; Lagzian, Shirin [Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 2015, vol. 45, # 3, p. 350 - 355]
[21]Nobuta, Tomoya; Xiao, Guozhi; Ghislieri, Diego; Gilmore, Kerry; Seeberger, Peter H. [Chemical Communications, 2015, vol. 51, # 82, p. 15133 - 15136]
[22]Morodo, Romain; Gérardy, Romaric; Petit, Guillaume; Monbaliu, Jean-Christophe M. [Green Chemistry, 2019, vol. 21, # 16, p. 4422 - 4433]
[23]Bach, Long Giang; Le, Van Thuan; Nguyen, Tan Tai; Nguyen, Thi Anh Nga; Nguyen, Thi Thuong; Nguyen, Trinh Duy; Tran, Nguyen Hai Tai; Tran, Vy Anh; Vo, The Ky; Vo, Thu-Thao Thi [Journal of Chemistry, 2020, vol. 2020]
[24]Chaudhary, Garima; Gupta, Neha; Singh, Amit Pratap [Polyhedron, 2021, vol. 207]

9
[ 2461-42-9 ]
[ 36112-95-5 ]

Yield	Reaction Conditions	Operation in experiment
46%	With perchloric acid In water at 80℃;
	With base or acid
	With sulfuric acid for 1h; Ambient temperature;

Reference： [1]Dishong, Dennis M.; Diamond, Craig J.; Cinoman, Michael I.; Gokel, Geoge W. [Journal of the American Chemical Society, 1983, vol. 105, # 3, p. 586 - 593]
[2]Wang; Chen; Liu; Wong [Tetrahedron Letters, 1989, vol. 30, # 15, p. 1917 - 1920]
[3]Ohta, Hiromichi; Miyamae, Yoshitaka; Tsuchihashi, Gen-ichi [Agricultural and Biological Chemistry, 1989, vol. 53, # 1, p. 215 - 222]

10
[ 2461-42-9 ]
[ 87102-64-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium azide; ammonium chloride In methanol; water Heating;
72.4%	With sodium azide; ammonium chloride In water for 0.5h; Heating;
	With sodium azide; ammonium chloride In methanol

	With sodium azide; ammonium chloride
	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane With sodium azide In ethanol; water for 1h; Stage #2: With tetrabutylammomium bromide In ethanol; water	2.2.2. General synthesis of 1-azido-3-(aryl) propane-2-ol (4a-f) General procedure: NaN 3 (0.03 mol) and 2-(Aryloxymethyl)oxiranes ( 3a-f ) (0.01 mol) were dissolved in ethanol and water mixture in the ratio of 50:50 vol% and stirred for 1 h. Subsequently, a pinch of tetrabutylammonium bromide (TBAB) was introduced to the above mixture to improve the completeness of the reaction. The obtained product was treated with ice-cold water and separated with ethyl acetate. Finally, the obtained 1-azido-3-(aryl) propan-2-ol ( 4 a-f ) product was dried in an oven under a vacuum.

Reference： [1]Pchelka, Beata; Radomska, Justyna; Plenkiewicz, Jan [Synthetic Communications, 1998, vol. 28, # 23, p. 4355 - 4364]
[2]Oatis, J. E.; Baker, J. P.; McCarthy, J. R.; Knapp, D. R. [Journal of Medicinal Chemistry, 1983, vol. 26, # 12, p. 1687 - 1691]
[3]Pchelka, Beata Krystyna; Loupy, Andre; Plenkiewicz, Jan; Blanco, Luis [Tetrahedron Asymmetry, 2000, vol. 11, # 13, p. 2719 - 2732]
[4]Pamies; Baeckvall [Journal of Organic Chemistry, 2001, vol. 66, # 11, p. 4022 - 4025]
[5]Sarojini, Perumal; Jeyachandran, Malaichamy; Sriram, Dharmarajan; Ranganathan, Palraj; Gandhimathi [Journal of Molecular Structure, 2021, vol. 1233]

11
[ 30389-33-4 ]
[ 106-89-8 ]
[ 2461-42-9 ]
[ 51781-13-6 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 100 - 106

12
[ 2461-42-9 ]
[ 841-77-0 ]
1-(4-benzhydrylpiperazin-1-yl)-3-(naphthalen-1-yloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane; diphenylmethylpiperazine With aluminium(III) triflate In toluene at 70℃; for 5h; Stage #2: With sodium hydrogencarbonate In water; toluene regioselective reaction;
87%	In ethanol for 1h; Reflux;	7 1-(4-diphenylmethylpiperazinyl)-3-(1-naphthyloxy)-propan-2-ol (HUHS1011) Example 7 1-(4-diphenylmethylpiperazinyl)-3-(1-naphthyloxy)-propan-2-ol (HUHS1011) To a solution of 2-((1-naphthyloxy)methyl)oxirane (50 mg, 0.25 mmol) in ethanol (0.50 mL) was added 4-diphenylmethylpiperazine (76 mg, 0.30 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1011 (98 mg, 87%). 1H-NMR (400 MHz, acetone-d6) δ 2.60-2.71 (m, 3H), 2.82-2.94 (m, 7H), 4.15 (dd, J=10.5 and 5.0 Hz, 1H), 4.21-4.25 (m, 2H), 4.28 (s, 1H), 6.96 (d, J=7.4 Hz, 1H), 7.18 (d, t, J=7.3 Hz, 2H), 7.29 (t, J=7.3 Hz, 4H), 7.39 (t, J=7.8 Hz, 1H), 7.44-7.51 (m, 7H), 7.83-7.85 (m, 1H), 8.80 (d, J=8.2 Hz, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C30H33N2O2 ([M+H+]): 453.2537. Found 453.2553.
87%	In ethanol at 20℃; for 1h;	7 Example 7: 1-(4-diphenylmethylpiperazinyl)-3-(1-naphthyloxy)-propan-2-ol (HUHS 1011) 2-((1-naphthyloxy)methyl) (50 mg, 0.25 mmol) in ethanol (76 mg, 0.30 mmol) of 4 - (0.50 ml) solution of the oxysilane at room temperature was added Diphenylmethylpiperazine. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (98 mg, 87%) was obtained by silica gel column chromatography of the crude product was purified HUHS1011.

In ethanol for 3h; Heating;

Reference： [1]Williams, D. Bradley G.; Cullen, Adam [Journal of Organic Chemistry, 2009, vol. 74, # 24, p. 9509 - 9512]
[2]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0209-0211
[3]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0094-0096
[4]Suzuki, Tsuneji; Fukazawa, Nobuyuki; San-nohe, Kunio; Sato, Wakao; Yano, Osamu; Tsuruo, Takashi [Journal of Medicinal Chemistry, 1997, vol. 40, # 13, p. 2047 - 2052]

13
[ 2461-42-9 ]
[ 71-30-7 ]
4-amino-1-[2-hydroxy-3-(naphthalen-1-yloxy)-propyl]-1<i>H</i>-pyrimidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: Cytosine With potassium carbonate In N,N-dimethyl-formamide at 105 - 110℃; Stage #2: 3-(1-naphthyloxy)-1,2-epoxypropane In N,N-dimethyl-formamide at 105 - 110℃;

Reference： [1]Ozerov; Novikov; Brel' [Chemistry of Heterocyclic Compounds, 1999, vol. 35, # 1, p. 78 - 83]

14
[ 2461-42-9 ]
[ 134461-75-9 ]
1-(6-amino-purin-9-yl)-3-(naphthalen-1-yloxy)-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: adenine With potassium carbonate In N,N-dimethyl-formamide at 105 - 110℃; for 1h; Stage #2: 3-(1-naphthyloxy)-1,2-epoxypropane In N,N-dimethyl-formamide at 105 - 110℃;

Reference： [1]Ozerov; Novikov; Brel' [Chemistry of Heterocyclic Compounds, 1999, vol. 35, # 1, p. 78 - 83]

15
[ 2461-42-9 ]
1-hydroxy-3-(naphthalen-1-yloxy)-propan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With ammonium heptamolybdate; dihydrogen peroxide In tetrahydrofuran at 20℃; for 1h;

Reference： [1]Ismail, Nusrat; Rao, R. Nageswara [Chemistry Letters, 2000, # 7, p. 844 - 845]

16
[ 2461-42-9 ]
[ 143-33-9 ]
[ 20804-76-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With ammonium chloride In methanol; water at 85℃; for 15h;
70%	In ethanol; water at 20℃; for 15h;
	In ethanol; water at 20℃; for 18h;

Reference： [1]Pàmies, Oscar; Bäckvall, Jan-E. [Advanced Synthesis and Catalysis, 2001, vol. 343, # 6-7, p. 726 - 731]
[2]Kamal, Ahmed; Khanna, G.B. Ramesh [Tetrahedron Asymmetry, 2001, vol. 12, # 3, p. 405 - 410]
[3]Kamal, Ahmed; Khanna, G.B. Ramesh; Krishnaji; Tekumalla, Venkatesh; Ramu [Tetrahedron Asymmetry, 2005, vol. 16, # 8, p. 1485 - 1494]

17
[ 2461-42-9 ]
[ 61249-00-1 ]
[ 61249-00-1 ]
[ 61248-78-0 ]

Yield	Reaction Conditions	Operation in experiment
42%	With (1R,2R)-(-)-N,N'-bis(3,5-di-tert-butylsalicydene)-1,2-cyclohexanediaminocobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;

Reference： [1]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]

18
[ 2461-42-9 ]
[ 61249-00-1 ]
[ 61249-00-1 ]
[ 56715-19-6 ]

Yield	Reaction Conditions	Operation in experiment
42%	With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;

Reference： [1]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]

19
[ 2461-42-9 ]
[ 61249-00-1 ]
[ 61248-78-0 ]
[ 56715-19-6 ]

Yield	Reaction Conditions	Operation in experiment
57%	With water In tetrahydrofuran at 0 - 20℃; for 60h; Resolution of racemate;
38%	With (1R,2R)-(-)-N,N'-bis(3,5-di-tert-butylsalicydene)-1,2-cyclohexanediaminocobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃; for 48h;
1: 99 % ee 2: 88 % ee	With Bacillus megaterium ECU₁₀₀₁ epoxide hydrolase, M₁₄₅A mutant for 16h; Resolution of racemate; Enzymatic reaction;	Chemoenzymatic Synthesis of (S)-Propranolol. Gram-scale bioresolution ofNGE was conducted by mixing crude enzyme extracted from ∼5 g of fresh cellpellets and 4 g of racemic NGE in a 500 mL conical flask. The reaction wasterminated at ∼16 h, and the mixture was saturated by adding sodiumchloride followed by extracting with ethyl acetate (150 mL × 3). The resultantmixture with ees of 99% and eep of 91% was purified by using a silicagel column, affording the enantiomerically pure epoxide (99% ee) and opticallyenriched diol (88% ee).

Reference： [1]Zhu, Chengfeng; Yuan, Guozan; Chen, Xu; Yang, Zhiwei; Cui, Yong [Journal of the American Chemical Society, 2012, vol. 134, # 19, p. 8058 - 8061]
[2]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]
[3]Kong, Xu-Dong; Yuan, Shuguang; Li, Lin; Chen, She; Xu, Jian-He; Zhou, Jiahai [Proceedings of the National Academy of Sciences of the United States of America, 2014, vol. 111, # 44, p. 15717 - 15722]

20
[ 2461-42-9 ]
[ 61249-00-1 ]
[ 61248-78-0 ]
[ 56715-19-6 ]

Yield	Reaction Conditions	Operation in experiment
43%	With water In tetrahydrofuran; dichloromethane at 20℃; for 6h;
42%	With water In tetrahydrofuran; dichloromethane at 20℃; for 5h;
38%	With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃; for 48h;

Reference： [1]Thakur, Santosh Singh; Chen, Shu-Wei; Li, Wenji; Shin, Chang-Kyo; Kim, Seong-Jin; Koo, Yoon-Mo; Kim, Geon-Joong [Journal of Organometallic Chemistry, 2006, vol. 691, # 9, p. 1862 - 1872]
[2]Thakur, Santosh Singh; Chen, Shu-Wei; Li, Wenji; Shin, Chang-Kyo; Koo, Yoon-Mo; Kim, Geon-Joong [Synthetic Communications, 2006, vol. 36, # 16, p. 2371 - 2383]
[3]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]

21
[ 2461-42-9 ]
[ 4248-19-5 ]
[ 61249-00-1 ]
[(S)-2-hydroxy-3-(naphthalen-1-yloxy)propyl]carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With air; 4-nitro-benzoic acid In various solvent(s) at 20℃; for 24h;

Reference： [1]Bartoli, Giuseppe; Bosco, Marcella; Carlone, Armando; Locatelli, Manuela; Melchiorre, Paolo; Sambri, Letizia [Organic Letters, 2004, vol. 6, # 22, p. 3973 - 3975]

22
[ 2461-42-9 ]
[ 61249-00-1 ]
[ 61248-78-0 ]

Yield	Reaction Conditions	Operation in experiment
1: 46% 2: 50%	With C₇₂H₁₀₂Co₂F₁₂N₄O₁₂P₂; water In tetrahydrofuran at 0 - 20℃; for 18h; optical yield given as %ee;
1: 48% 2: 48%	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane With C₅₇H₅₄CoN₃O₈ In dichloromethane at 20℃; for 0.25h; Stage #2: With water In dichloromethane at 20℃; for 6h; Cooling with ice; enantioselective reaction;
1: 47% 2: 43%	With water at 20℃; for 24h;

1: 45% 2: 45%	With (S,S)-(salen)cobalt(III)(OAc) In water at 20℃; for 24h;
1: 42.4% 2: 45.3%	With Recombinant whole cells (1.0g dry cell weight) harboring BmEH_F₁₂₈T; tween-80 In aq. phosphate buffer; 2,2,4-trimethylpentane at 25℃; for 8.16667h; Green chemistry; Enzymatic reaction;	2.6 Preparative bioresolution of rac-1 For the up-scaled bioresolution of epoxide 1, the reaction was performed in a 250-mL three-neck flask. Recombinant whole cells (1.0g dry cell weight) harboring BmEHF128T was added to 50 mL of potassium phosphate buffer (100 mM, pH 7.0) and rehydrated at 25°C for 10 min. Another 50 mL of buffer containing 0.8% Tween-80 (w/v) was mixed with 100 mL of organic phase (diisopropyl ether/isooctane=65/35, v/v) containing 20 g of rac-1 and stirred vigorously in the flask, resulting in a water/oil emulsion. The rehydrated biocatalyst was added before the reaction mixture was mechanically agitated at 180 rpm for 8 h at room temperature (25°C). Once the ee value of residual epoxide reached 99% (S), the reaction mixture was centrifuged to separate the organic phase containing the residual (S)-epoxide, the aqueous phase and the precipitate containing the (R)-diol and cell pellets. The diol precipitate was washed with water and petroleum ether in turn to remove the residual epoxide and recrystallized with ethanol, giving (R)-2 as a white crystal. The organic layer was dried over Na2SO4, filtered and the solvent was evaporated, the column chromatography of the residue afforded (S)-1 as a light yellow oil. (S)-α-Naphthyl glycidyl ether (1): yield, 45.3% (9.06 g); 99.1% ee; [α]25D25D: +37.0 (c 1.0, methanol), Lit. [15] [α]25D25D: +32.9 (c 1.0, methanol) with >95% ee. 1H NMR (400 MHz, CDCl3), δ/ppm: 8.28-8.30 (m, 1H), 7.75-7.78 (m, 1H), 7.44-7.47 (m, 3H), 7.40 (t, J=7.9 Hz, 1H), 6.71 (d, J=7.6 Hz, 1H), 4.29 (dd, J=2.9, 11.0 Hz, 1H), 4.03 (dd, J=5.6, 11.0, 1H), 3.40-3.41 (m, 1H), 2.88 (t, J=4.5 Hz, 1H), 2.76 (dd, J=2.6, 4.8 Hz, 1H). (R)-3-(1′-Naphthyloxy)-propane-1,2-diol (2): yield, 42.4% (9.24 g); >99.5% ee; [α]25D: -8.3 (c 1.2, ethanol), Lit. [22] [α]25D: -7.6 (c 1.2, ethanol) with 97% ee. 1H NMR (500 MHz, CDCl3), δ/ppm: 8.20-8.22 (m, 1H), 7.80-7.82 (m, 1H), 7.45-7.49 (m, 3H), 7.37 (t, J=8.0 Hz, 1H), 6.84 (d, J=7.5 Hz, 1H), 4.27-4.28 (m, 1H), 4.23-4.24 (m, 2H), 3.94 (dd, J=3.6, 11.2Hz, 1H), 3.86 (dd, J=n5.2, 11.2Hz, 1H), 2.21 (s, 2H).
1: 44.6% 2: 37.2%	With Bacillus megaterium epoxide hydrolase In aq. phosphate buffer; di-isopropyl ether at 25℃; Enzymatic reaction;
42%	With (1R,2R)-(-)-N,N'-bis(3,5-di-tert-butylsalicydene)-1,2-cyclohexanediaminocobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃; for 12h;
1: 42% 2: 42%	With water In tetrahydrofuran at 0 - 20℃; for 10h; Resolution of racemate; enantioselective reaction;
38%	With (1R,2R)-(-)-N,N'-bis(3,5-di-tert-butylsalicydene)-1,2-cyclohexanediaminocobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃; for 60h;
	With {μ-{{2,2'-{(1R,2R)-cyclohexane-1,2-diylbis[(nitrilo-κN)[4,6-bis(1,1-dimethylethyl)phenolato-κO:κO](2-)}}(dichloronickel)cobalt; water at 20℃; for 8h; optical yield given as %ee; enantioselective reaction;

Reference： [1]Sadhukhan, Arghya; Khan, Noor-Ul H.; Roy, Tamal; Kureshy, Rukhsana I.; Abdi, Sayed H. R.; Bajaj, Hari C. [Chemistry - A European Journal, 2012, vol. 18, # 17, p. 5256 - 5260]
[2]Tak, Rajkumar; Kumar, Manish; Menapara, Tusharkumar; Gupta, Naveen; Kureshy, Rukhsana I.; Khan, Noor-ul H.; Suresh [Advanced Synthesis and Catalysis, 2017, vol. 359, # 22, p. 3990 - 4001]
[3]Subhas Bose; Narsimha Reddy; Chavhan, Sanjay W. [Synthesis, 2005, # 14, p. 2345 - 2348]
[4]Kothakonda, Kiran Kumar; Bose, D. Subhas [Chemistry Letters, 2004, vol. 33, # 9, p. 1212 - 1213]
[5]Kong, Xu-Dong; Yu, Hui-Lei; Yang, Sheng; Zhou, Jiahai; Zeng, Bu-Bing; Xu, Jian-He [Journal of Molecular Catalysis B: Enzymatic, 2015, vol. 122, p. 275 - 281]
[6]Kong, Xu-Dong; Ma, Qian; Zhou, Jiahai; Zeng, Bu-Bing; Xu, Jian-He [Angewandte Chemie - International Edition, 2014, vol. 53, # 26, p. 6641 - 6644][Angew. Chem., 2014, p. 6759 - 6762,4]
[7]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]
[8]Roy, Tamal; Barik, Sunirmal; Kumar, Manish; Kureshy, Rukhsana I.; Ganguly, Bishwajit; Khan, Noor-Ul H.; Abdi, Sayed H. R.; Bajaj, Hari C. [Catalysis science and technology, 2014, vol. 4, # 11, p. 3899 - 3908]
[9]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]
[10]Location in patent: experimental part Kawthekar, Rahul B.; Kim, Geon-Joong [Helvetica Chimica Acta, 2008, vol. 91, # 2, p. 317 - 332]

23
[ 2461-42-9 ]
[ 61249-00-1 ]
[ 56715-19-6 ]

Yield	Reaction Conditions	Operation in experiment
42%	With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;
38%	With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃; for 48h;

Reference： [1]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]
[2]Schaus, Scott E.; Brandes, Bridget D.; Larrow, Jay F.; Tokunaga, Makoto; Hansen, Karl B.; Gould, Alexandra E.; Furrow, Michael E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315]

24
[ 92-54-6 ]
[ 2461-42-9 ]
[ 102654-83-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	In ethanol for 1h; Reflux;	1 3-(1-naphthyloxy)-1-(4-phenylpiperazinyl)propan-2-ol (HUHS1004) Example 1 3-(1-naphthyloxy)-1-(4-phenylpiperazinyl)propan-2-ol (HUHS1004) To a solution of 2-((1-naphthyloxy)methyl)oxirane (100 mg, 0.50 mmol) in ethanol (1 mL) was added 4-phenylpiperazine (92 μL, 0.60 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1004 (180 mg, 98%). 1H-NMR (400 MHz, CDCl3) δ2.65-2.71 (m, 2H), 2.73-2.76 (m, 2H), 2.87-2.92 (m, 2H), 3.20-3.29 (m, 4H), 4.16 (dd, J=9.6 and 5.0 Hz, 1H), 4.25 (dd, J=9.6 and 5.0 Hz, 1H), 4.28-4.34 (m, 1H), 6.84 (d, J=7.8 Hz, 1H), 6.86 (t, J=7.3 Hz, 1H), 6.95 (d, J=8.2 Hz, 2H), 7.28 (dd, J=8.3 and 7.3 Hz, 2H), 7.37 (t, J=7.3 Hz, 1H), 7.44 (d, J=8.2 Hz, 1H) 7.43-7.51 (m, 2H), 7.79-7.82 (m, 1H), 8.26-8.28 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C23H27N2O2 ([M+H+]): 363.2067. Found 363.2039.
98%	In ethanol at 20℃; for 1h;	1 Example 1: 3-(1-naphthyloxy)-1-(4-phenylpiperazinyl) propan-2-ol (HUHS 1004) 2-((1-naphthyloxy) methyl) (100 mg, 0.50 mmol) in ethanol (1 ml) solution of 4 - phenylpiperazine (92 μL, 0.60 mmol) of the apparatus is at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (180 mg, 98%) was obtained by silica gel column chromatography of the crude product was purified HUHS1004.
85.58%	In ethanol Heating;

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0188-0190
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0073-0075
[3]Xiao, Zhihui; Yuan, Mu; Zhang, Si; Wu, Jun; Qi, Shuhua; Li, Qingxin [Magnetic Resonance in Chemistry, 2005, vol. 43, # 10, p. 869 - 872]

25
[ 38212-30-5 ]
[ 2461-42-9 ]
1-(4-(4-methoxyphenyl)piperazinyl)-3-(1-naphthyloxyl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79.54%	In ethanol Heating;
72%	With N-ethyl-N,N-diisopropylamine In ethanol for 1h; Reflux;	3 1-(4-(4-methoxyphenyl)piperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1003) Reference Example 3 1-(4-(4-methoxyphenyl)piperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1003) To a solution of 2-((1-naphthyloxy)methyl)oxirane (75 mg, 0.38 mmol) in ethanol (1 mL) were added 4-(4-methoxyphenyl)piperazine (119 mg, 0.45 mmol) and diisoproethylamine (0.19 mL, 1.12 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1003 (104 mg, 72%). 1H-NMR (400 MHz, CDCl3) δ2.66-2.71 (m, 2H), 2.73-2.76 (m, 2H), 2.87-2.92 (m, 2H), 3.09-3.19 (m, 4H), 3.77 (s, 3H), 4.16 (dd, J=9.6 and 5.0 Hz, 1H), 4.24 (dd, J=9.6 and 5.0 Hz, 1H), 4.28-4.34 (m, 1H), 6.84-6.87 (m, 3H), 6.91-6.92 (m, 2H), 7.37 (t, J=8.2 Hz, 1H), 7.44-7.51 (m, 3H), 7.78-7.95 (m, 1H), 8.23-8.30 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C24H29N2O3 ([M+H+]): 393.2173. Found 393.2170.
72%	With N-ethyl-N,N-diisopropylamine In ethanol at 20℃; for 1h;	3 Reference Example 3: 1-(4-(4-methoxyphenyl)piperazinyl)-3-(1-naphthyloxy) propan-2-ol (HUHS 1003) 2-((1-naphthyloxy)methyl)4-(4-methoxyphenyl)piperazine (75 mg, 0.38 mmol) in ethanol (1 ml) solution of oxirane (119 mg, 0.45 mmol) (0.19 ml, 1.12 mmol) was added at room temperature and [...]. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (104 mg, 72%) was obtained by silica gel column chromatography of the crude product was purified HUHS1003.

Reference： [1]Xiao, Zhihui; Yuan, Mu; Zhang, Si; Wu, Jun; Qi, Shuhua; Li, Qingxin [Magnetic Resonance in Chemistry, 2005, vol. 43, # 10, p. 869 - 872]
[2]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0185-0187
[3]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0070-0072

26
[ 2461-42-9 ]
[ 39512-50-0 ]
[ 112551-82-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With N-ethyl-N,N-diisopropylamine In ethanol for 1h; Reflux;	10 1-(4-(2-chlorophenyl)piperazinyl)-3-(1-naphthyloxy)-propan-2-ol (HUHS1014) Example 10 1-(4-(2-chlorophenyl)piperazinyl)-3-(1-naphthyloxy)-propan-2-ol (HUHS1014) To a solution of 2-((1-naphthyloxy)methyl)oxirane (75 mg, 0.38 mmol) in ethanol (1.5 mL) were added 4-(2-chlorophenyl)piperazine (105 mg, 0.45 mmol) and diisoproethylamine (0.19 mL, 1.12 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1014 (129 mg, 86%). 1H-NMR (400 MHz, CDCl3) δ 2.62-2.80 (m, 4H), 2.92-2.98 (m, 2H), 3.08-3.15 (m, 4H), 4.15 (dd, J=9.6 and 5.0 Hz, 1H), 4.25 (dd, J=9.2 and 5.2 Hz, 1H), 4.29-4.34 (m, 1H), 6.85 (d, J=7.8 Hz, 1H), 6.99 (t, J=7.8 Hz, 1H), 7.06 (d, J=7.8 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 7.36-7.40 (m, 2H), 7.44-7.52 (m, 3H), 7.79-7.82 (m, 1H), 8.21-8.28 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C23H25ClN2O2Na ([M+Na+]): 419.1497. Found 419.1487.
86%	With N-ethyl-N,N-diisopropylamine In ethanol at 20℃; for 1h;	10 Example 10: 1-(4-(2-Chlorophenyl)piperazinyl)-3-(1-naphthyloxy)-propan-2-ol (HUHS 1014) 2-((1-naphthyloxy)methyl)4-(2-chlorophenyl)piperazine (75 mg, 0.38 mmol) in ethanol (1.5 ml) solution of oxirane (105 mg, 0.45 mmol) (0.19 ml, 1.12 mmol) was added at room temperature and [...]. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (129 mg, 86%) was obtained by silica gel column chromatography of the crude product was purified HUHS1014.
58.65%	In ethanol Heating;

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0218-0220
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0103-0105
[3]Xiao, Zhihui; Yuan, Mu; Zhang, Si; Wu, Jun; Qi, Shuhua; Li, Qingxin [Magnetic Resonance in Chemistry, 2005, vol. 43, # 10, p. 869 - 872]

27
[ 2461-42-9 ]
[ 16015-71-7 ]
1-(4-(3-methoxyphenyl)piperazinyl)-3-(1-naphthyloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	In ethanol for 1h; Reflux;	2 1-(4-(3-methoxyphenyl)piperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1002) Reference Example 2 1-(4-(3-methoxyphenyl)piperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1002) To a solution of 2-((1-naphthyloxy)methyl)oxirane (100 mg, 0.50 mmol) in ethanol (1 mL) was added 4-(3-methoxyphenyl)piperazine (104 μL, 0.60 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1002 (165 mg, 84%). 1H-NMR (400 MHz, CDCl3) δ2.63-2.77 (m, 4H), 2.84-2.89 (m, 2H), 3.19-3.28 (m, 4H), 3.79 (s, 3H), 4.16 (dd, J=9.6 and 5.0 Hz, 1H), 4.24 (dd, J=9.6 and 5.0 Hz, 1H), 4.27-4.33 (m, 1H), 6.43 (dd, J=8.2 and 1.8 Hz, 1H), 6.48 (t, J=1.8 Hz, 1H), 6.56 (dd, J=8.2 and 1.8 Hz, 1H), 6.84 (d, J=6.8 Hz, 1H), 7.18 (t, J=8.2 Hz, 1H), 7.37 (t, J=8.2 Hz, 1H), 7.45 (d, J=8.2 Hz, 1H), 7.45-7.51 (m, 2H), 7.78-7.81 (m, 1H), 8.25-8.28 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C24H29N2O3 ([M+H+]): 393.2173. Found 393.2149.
84%	In ethanol at 20℃; for 1h;	2 Reference Example 2: 1-(4-(3-methoxyphenyl)piperazinyl)-3-(1-naphthyloxy) propan-2-ol (HUHS 1002) 2-((1-naphthyloxy) methyl)4-(3-methoxyphenyl) piperazine (100 mg, 0.50 mmol) in ethanol (1 ml) solution of oxirane (104 μL, 0.60 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (165 mg, 84%) was obtained by silica gel column chromatography of the crude product was purified HUHS1002.
78.31%	In ethanol Heating;

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0182-0184
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0067-0069
[3]Xiao, Zhihui; Yuan, Mu; Zhang, Si; Wu, Jun; Qi, Shuhua; Li, Qingxin [Magnetic Resonance in Chemistry, 2005, vol. 43, # 10, p. 869 - 872]

28
[ 2461-42-9 ]
[ 35386-24-4 ]
[ 57149-07-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	In ethanol for 1h; Reflux;	1 Synthesis of (RS)-naftopidil (HUHS1001) Reference Example 1 Synthesis of (RS)-naftopidil (HUHS1001) To a solution of 2-((1-naphthyloxy)methyl)oxirane (100 mg, 0.50 mmol) in ethanol (1 mL) was added 4-(2-methoxyphenyl)piperazine (95 μL, 0.60 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give (RS)-naftopidil (199 mg, 100%). 1H-NMR (400 MHz, CDCl3) δ 2.72-2.76 (m, 4H), 2.92-2.95 (m, 2H), 3.09-3.18 (m, 4H), 3.87 (s, 3H), 4.16 (dd, J=9.6 and 5.0 Hz, 1H), 4.24 (dd, J=9.6 and 5.0 Hz, 1H), 4.28-4.34 (m, 1H), 6.84 (d, J=7.8 Hz, 1H), 6.87 (d, J=7.8 Hz, 1H), 6.91-6.98 (m, 2H), 7.00-7.04 (m, 1H), 7.39 (t, J=8.2 Hz, 1H), 7.44 (d, J=8.2 Hz, 1H), 7.47-7.51 (m, 2H), 7.79-7.81 (m, 1H), 8.26-8.29 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C24H29N2O3 ([M+H+]): 393.2173. Found 393.2148.
100%	In ethanol at 20℃; for 1h;	1 Reference example 1: synthesis of (RS)-(HUHS1001) naftopidil 2-((1-naphthyloxy)methyl)4-(2-methoxyphenyl) piperazine (100 mg, 0.50 mmol) in ethanol (1 ml) solution of oxirane (95 μL, 0.60 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (RS)- (199 mg, 100%) of crude product was purified by silica gel column chromatography to give naftopidil.
92%	With zinc(II) perchlorate hexahydrate In dichloromethane at 20℃; for 16h;

		1 Preparation of 1-(2-Methoxyphenyl)-4-[3-(naphth-1-yloxy)-2-hydroxypropyl]-piperazine EXAMPLE 1 Preparation of 1-(2-Methoxyphenyl)-4-[3-(naphth-1-yloxy)-2-hydroxypropyl]-piperazine A mixture of 30.0 g. (0.15 mol) 2,3-epoxy-1-(1-naphthyloxy)-propane and 28.8 g. (0.15 mol) 1-(2-methoxy-phenyl)-piperazine was heated to 120° C. and maintained at this temperature for 5 hours. After cooling, a red solidified product was obtained which was recrystallized from isopropanol and had a melting point of 125° - 126° C.
95 %Chromat.	With zinc(II) perchlorate In water at 140℃; for 0.166667h; Flow reactor;

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0179-0181
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0064-0066
[3]Shivani; Pujala, Brahmam; Chakraborti, Asit K. [Journal of Organic Chemistry, 2007, vol. 72, # 10, p. 3713 - 3722]
[4]Current Patent Assignee: ROCHE HOLDING AG; C.H. Boehringer Sohn AG & Co. KG - US3997666, 1976, A
[5]Morodo, Romain; Gérardy, Romaric; Petit, Guillaume; Monbaliu, Jean-Christophe M. [Green Chemistry, 2019, vol. 21, # 16, p. 4422 - 4433]

29
[ 2461-42-9 ]
[ 4039-82-1 ]
1-(1-naphthalenyloxy)-3-(4-benzyloxymethyl-[1,2,3]triazol-1-yl)-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With copper(l) iodide; sodium azide In various solvent(s) at 20℃; for 16h;

Reference： [1]Kumaraswamy, Gullapalli; Ankamma, Kukkadapu; Pitchaiah, Arigala [Journal of Organic Chemistry, 2007, vol. 72, # 25, p. 9822 - 9825]

30
[ 316141-37-4 ]
[ 2461-42-9 ]
(2-{1-[2-hydroxy-3-(naphthalen-1-yloxy)-propyl]-1H-[1,2,3]triazol-4-yl}pyrrolidin-1-yl)carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 9822 - 9825

31
[ 2461-42-9 ]
[ 536-74-3 ]
1-(naphthalen-2-yloxy)-3-(4-phenyl-[1,2,3]triazol-1-yl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium azide at 80℃; for 9h; Green chemistry;	General experimental procedure1 for the synthesis ofbeta-hydroxy triazoles 3 General procedure: An equimolar mixture of epoxides 1 and NaN3 wasstirred for 10 min in 1 g of IL i.e. [bmim]Br, loaded withCu(I) at 5 mol% w.r.t. reactant concentration. To theresultant, were added an equimolar ratio of terminalalkynes 2 via a syringe and the reaction was furthermaintained under stirring at 80 8C for a specified period oftime. After completion of the reaction (as indicated byTLC), 10 mL of distilled water were added under continuousstirring, and solid crude product obtained was simplycollected by filtration. Purification of crude products wascarried out by recrystallization from ethanol. The filtratecontaining IL and the Cu(I) catalyst was immediatelyreduced under low pressure and further dried at 100 8C for20-30 min in a hot air oven, for the consecutive reactionruns. Physical data of some representative compounds aregiven below.
90%	With copper(l) iodide; sodium azide In various solvent(s) at 20℃; for 16h;

Reference： [1]Singh, Nasseb [Comptes Rendus Chimie, 2015, vol. 18, # 12, p. 1257 - 1263]
[2]Kumaraswamy, Gullapalli; Ankamma, Kukkadapu; Pitchaiah, Arigala [Journal of Organic Chemistry, 2007, vol. 72, # 25, p. 9822 - 9825]

32
[ 2461-42-9 ]
2-((naphthalen-4-yloxy)methyl)thiirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With ammonium thiocyanate at 90℃; for 0.166667h; Neat (no solvent);
90%	With ammonium thiocyanate In water for 0.75h; Microwave irradiation;
85%	With potassium thioacyanate In acetonitrile at 20℃; for 0.75h;

65%

With thiourea In methanol for 1.5h; Reflux;

Reference： [1]Location in patent: experimental part Akhlaghinia, Batool; Rahimizadeh, Mohammad; Eshghi, Hosein; Zhaleh, Sara; Rezazadeh, Soodabeh [Journal of Sulfur Chemistry, 2012, vol. 33, # 3, p. 351 - 361]
[2]Location in patent: experimental part Chen, Hsing-Ming; Chen, Po-Yuan; Wang, Chih-Feng; Tsai, Jui-Chi; Wang, Eng-Chi [ARKIVOC, 2012, vol. 2012, # 8, p. 157 - 168]
[3]Reddy, Ch. Sanjeeva; Nagavani [Heteroatom Chemistry, 2008, vol. 19, # 1, p. 97 - 99]
[4]Dong, Jun; Xu, Jiaxi [New Journal of Chemistry, 2018, vol. 42, # 11, p. 9037 - 9044]

33
[ 2461-42-9 ]
[ 61249-00-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 43 percent / water / (R,R)-salen-Co(III)OAc complex / 24 h / 20 °C 2: 85 percent / DIAD; triphenylphosphine / benzene / Heating
	Multi-step reaction with 2 steps 1: 45 percent / (R,R)-salen cobalt(III) OAc complex / H₂O / 24 h / 20 °C 2: 87 percent / DEAD; TPP / benzene / 24 h / Heating
	Multi-step reaction with 3 steps 1: Ambient temperature 2: water, NaOH / 52 h / Ambient temperature; Lipase PS "Amano", phosphate buffer (pH 7) 3: 20 percent aq. NaOH / propan-2-ol / Ambient temperature

Multi-step reaction with 2 steps 1.1: Recombinant whole cells (1.0g dry cell weight) harboring BmEH_F₁₂₈T; tween-80 / aq. phosphate buffer; 2,2,4-trimethylpentane / 8.17 h / 25 °C / pH 7 / Green chemistry; Enzymatic reaction 2.1: hydrogen bromide; acetic acid / 1 h / 50 °C 2.2: 0.5 h / 25 °C

Reference： [1]Subhas Bose; Narsimha Reddy; Chavhan, Sanjay W. [Synthesis, 2005, # 14, p. 2345 - 2348]
[2]Kothakonda, Kiran Kumar; Bose, D. Subhas [Chemistry Letters, 2004, vol. 33, # 9, p. 1212 - 1213]
[3]Bevinakatti; Banerji [Journal of Organic Chemistry, 1991, vol. 56, # 18, p. 5372 - 5375]
[4]Kong, Xu-Dong; Yu, Hui-Lei; Yang, Sheng; Zhou, Jiahai; Zeng, Bu-Bing; Xu, Jian-He [Journal of Molecular Catalysis B: Enzymatic, 2015, vol. 122, p. 275 - 281]

34
[ 2461-42-9 ]
[ 4199-09-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 47 percent / water / (R,R)-salen-Co(III)OAc complex / 24 h / 20 °C 2: water / 12 h / 20 °C
	Multi-step reaction with 2 steps 1.1: 95 percent / p-nitrobenzoic acid; air / (S,S)-((t-Bu)4-salen)Co(II) / various solvent(s) / 24 h / 20 °C 2.1: CF₃CO₂H / CH₂Cl₂ / 1 h / 20 °C 2.2: 96 percent / H₂ / PtO₂ / methanol / 4 h / 20 °C / 760 Torr
	Multi-step reaction with 3 steps 1.1: CaCl₂ / acetonitrile 1.2: 93 percent / acetonitrile 2.1: 98.7 percent / Et₃N / CH₂Cl₂ 3.1: TFA / CH₂Cl₂ / 2 h

	Multi-step reaction with 4 steps 1: sodium azide; ammonium chloride 2: Novozym-435 (Candida antarctica Lipase B) / H(OC₅Ph₄)2Ru₂(H)(CO)4 / toluene / 72 h / 80 °C 3: LiOH / methanol / 2 h / 20 °C 4: 253 mg / 3-Angstroem molecular sieves; hydrogen / PtO₂ / methanol / 4 h / 20 °C / 750.08 Torr
	Multi-step reaction with 3 steps 1: (salen)CrN₃ complex (R,R)-1 / 0 - 2 °C 2: CSA / ethanol / 2 h / Ambient temperature 3: H₂ / PtO₂ / 4 h / Ambient temperature
	Multi-step reaction with 4 steps 1: Ambient temperature 2: water, NaOH / 52 h / Ambient temperature; Lipase PS "Amano", phosphate buffer (pH 7) 3: 20 percent aq. NaOH / propan-2-ol / Ambient temperature 4: water / Ambient temperature
	Multi-step reaction with 2 steps 1: Recombinant whole cells (1.0g dry cell weight) harboring BmEH_F₁₂₈T; tween-80 / aq. phosphate buffer; 2,2,4-trimethylpentane / 8.17 h / 25 °C / pH 7 / Green chemistry; Enzymatic reaction 2: 24 h / Reflux
	Multi-step reaction with 2 steps 1.1: C₆₅H₅₆CoN₃O₈ / dichloromethane / 0.17 h / 27 - 28 °C 1.2: 27 - 28 °C 2.1: Na-zeolite / acetonitrile / 20 °C
	Multi-step reaction with 2 steps 1.1: C₅₇H₅₄CoN₃O₈ / dichloromethane / 0.25 h / 20 °C 1.2: 6 h / 20 °C / Cooling with ice 2.1: Na-zeolite / acetonitrile / 20 °C

Reference： [1]Subhas Bose; Narsimha Reddy; Chavhan, Sanjay W. [Synthesis, 2005, # 14, p. 2345 - 2348]
[2]Bartoli, Giuseppe; Bosco, Marcella; Carlone, Armando; Locatelli, Manuela; Melchiorre, Paolo; Sambri, Letizia [Organic Letters, 2004, vol. 6, # 22, p. 3973 - 3975]
[3]Kawamoto; Wills [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2001, # 16, p. 1916 - 1928]
[4]Pamies; Baeckvall [Journal of Organic Chemistry, 2001, vol. 66, # 11, p. 4022 - 4025]
[5]Larrow, Jay F.; Schaus, Scott E.; Jacobsen, Eric N. [Journal of the American Chemical Society, 1996, vol. 118, # 31, p. 7420 - 7421]
[6]Bevinakatti; Banerji [Journal of Organic Chemistry, 1991, vol. 56, # 18, p. 5372 - 5375]
[7]Kong, Xu-Dong; Yu, Hui-Lei; Yang, Sheng; Zhou, Jiahai; Zeng, Bu-Bing; Xu, Jian-He [Journal of Molecular Catalysis B: Enzymatic, 2015, vol. 122, p. 275 - 281]
[8]Tak, Rajkumar; Kumar, Manish; Menapara, Tusharkumar; Gupta, Naveen; Kureshy, Rukhsana I.; Khan, Noor-ul H.; Suresh [Advanced Synthesis and Catalysis, 2017, vol. 359, # 22, p. 3990 - 4001]
[9]Tak, Rajkumar; Kumar, Manish; Menapara, Tusharkumar; Gupta, Naveen; Kureshy, Rukhsana I.; Khan, Noor-ul H.; Suresh [Advanced Synthesis and Catalysis, 2017, vol. 359, # 22, p. 3990 - 4001]

35
[ 2461-42-9 ]
[ 60148-34-7 ]

Yield	Reaction Conditions	Operation in experiment
43%	With periodic acid In 1,4-dioxane; water at 55℃; for 1.5h;
	Multi-step reaction with 2 steps 1: 1N sulfuric acid / 1 h / Ambient temperature 2: NaIO₄ / H₂O / 1 h / Ambient temperature
	Multi-step reaction with 2 steps 1: base or acid 2: NaIO₄

Reference： [1]Location in patent: experimental part Shapenova; Belyatskii; Panicheva [Russian Journal of Organic Chemistry, 2010, vol. 46, # 7, p. 1017 - 1020]
[2]Ohta, Hiromichi; Miyamae, Yoshitaka; Tsuchihashi, Gen-ichi [Agricultural and Biological Chemistry, 1989, vol. 53, # 1, p. 215 - 222]
[3]Wang; Chen; Liu; Wong [Tetrahedron Letters, 1989, vol. 30, # 15, p. 1917 - 1920]

36
[ 2461-42-9 ]
[ 62618-09-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine / ethanol / 4 h / Heating 2: conc. aq. HCl / ethanol / 6 h / Heating
	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane With ammonia In water at 40℃; for 0.233333h; Microwave irradiation; Stage #2: With hydrogenchloride In water; ethyl acetate	11.6 (6) Synthesis of 1-amino-3-(1-naphthoxy)-2-propanol 450mL concentrated aqueous ammonia was placed in a reaction flask special for microwave, then 3.0g 1-naphthyl epoxypropyl ether was added, and the reaction was performed at 40°C under magnetic stirring and 300W microwave irradiation for 14min. After the completion of the reaction, the reaction mixture was concentrated to dryness, then ethyl acetate was added, and the pH was adjusted to acidic with concentrated hydrochloride. After sucking filtration, 1-amino-3-(1-naphthoxy)-2-propanol hydrochloride was obtained, and then dried to result in a white solid. The solid was dissolved in water by heating, and the pH was adjusted to alkaline.

Reference： [1]Erhardt; Woo; Gorczynski; Anderson [Journal of Medicinal Chemistry, 1982, vol. 25, # 12, p. 1402 - 1407]
[2]Current Patent Assignee: NORTH-WEST UNIVERSITY (SOUTH AFRICA); NORTHWEST UNIVERSITY (CHINA) - EP2019090, 2009, A1 Location in patent: Page/Page column 11

37
[ 90-15-3 ]
[ 115314-14-2 ]
[ 2461-42-9 ]

Yield	Reaction Conditions	Operation in experiment
96.5%	With cesium fluoride; In water; N,N-dimethyl-formamide;	EXAMPLE 3 1-Naphthol (1.0 g) was dissolved in DMF (8 ml) under nitrogen atmosphere and the solution was cooled to 0 C. 25 Cesium fluoride (2.1 g) was added thereto and the mixture was stirred for 1 hour. Then, (S)-glycidyl m-nitrobenzenesulfonate (1.80 g, 99.3% e.e.) was added thereto and the mixture was stirred for 24 hours at the same temperature. After the reaction water was added to the mixture, the mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, condensed and the residue was subjected to silica gel chromatography (hexane/ethyl acetate; 6:1) to give 1.34 g of (S)-1-(2,3-epoxypropoxy)naphthalene (yield 96.5%, optical purity 99.2% e.e.) as a colorless oil. [alpha]D (21 C., c=1.0, CHCl3)=+16.9 NMR(CDCl3) delta:2.85(1H, m), 2.96(1H, m), 3.43-3.51(1H, m), 4.11(1H, dd), 4.40(1H, m), 6.80(1H, d), 7.32-7.52(4H, m), 7.74-7.83(1H, m), 8.24-8.34(2H, m)
96.5%	With cesium fluoride; In water; N,N-dimethyl-formamide;	EXAMPLE 4 1-Naphthol (1.0 g) was dissolved in DMF (8 ml) under nitrogen atmosphere and the solution was cooled to 0 C. Cesium fluoride (2.11 g) was added thereto and the mixture was stirred for 1 hour. Then, (S)-glycidyl m-nitrobenzenesulfonate (1.80 g, 99.3% e.e.) was added thereto and the mixture was stirred for 24 hours at the same temperature. After the reaction, water was added to the mixture, the mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, condensed and the residue was subjected to silica gel chromatography (hexane/ethyl acetate; 6:1) to give 1.34 g of (S)-1-(2,3-epoxypropoxy)naphthalene (yield 96.5%, optical purity 99.2% e.e.) as a colorless oil. [alpha]D (21 C., c=1.0, CHCl3)=+16.9 NMR(CDCl3) delta:2.85(1H, m), 2.96(1H, m), 3.43-3.51(1H, m), 4.11(1H, dd), 4.40(1H, m), 6.80(1H, d), 7.32-7.52(4H, m), 7.74-7.83(1H, m), 8.24-8.34(2H, m)
		Step a) 2-[(1-Naphthyloxy)methyl]oxirane The title compound was prepared from 1-naphthol and (2 S)-oxiranylmethyl 3-nitrobenzenesulfonate in substantially the same manner as described in example 21, step a. The product was obtained as an oil: MS mlz 200 M+.

Reference： [1]Patent: US6057476,2000,A
[2]Patent: US6087512,2000,A
[3]Patent: US2002/32222,2002,A1

38
[ 158151-65-6 ]
ethyl 2-piperazinylbenzoate monoacetate [ No CAS ]
[ 2461-42-9 ]
3-[4-(2-carbethoxyphenyl)piperazinyl]-1-(1-naphthyloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In 1,4-dioxane	4 3-[4-(2-Carboxyphenyl)piperazinyl]-1-(1-naphthyloxy)propan-2-ol Example 4 3-[4-(2-Carboxyphenyl)piperazinyl]-1-(1-naphthyloxy)propan-2-ol A mixture of ethyl 2-piperazinylbenzoate monoacetate (1.47 g) as obtained in Reference Example 1, 1-naphthyloxymethyloxirane (1.0 g) as obtained by the same reaction procedure as described in Reference Example 2, triethylamine (0.8 ml), and dioxane (50 ml) is refluxed for 4 hours. This reaction mixture is treated as in Example 1 and the residue is subjected to silica gel chromatography using ethyl acetate-hexane (1:3) to give 3-[4-(2-carbethoxyphenyl)piperazinyl]-1-(1-naphthyloxy)propan-2-ol (1.3 g) as brown oil.

Reference： [1]Current Patent Assignee: SENJU PHARMACEUTICAL CO.,LTD. - US5981530, 1999, A

39
[ 2217-40-5 ]
[ 2461-42-9 ]
[ 131812-95-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In ethanol; isopropyl alcohol	3 EXAMPLE 3 EXAMPLE 3 A solution of 1-aminotetralin (2.65 g) and 1-naphthyloxy-2,3-epoxypropane (3.6 g) in absolute ethanol (80 ml) is refluxed for 6 hours, the reaction solvent is then evaporated off under reduced pressure and the obtained oil is purified by silica gel column chromatography eluding with ethyl acetate up to complete elution of the reaction product. Fractions containing the desired product are pooled and evaporated under reduced pressure. The obtained product is dissolved in isopropanol (40 ml) and the solution is acidified by the addition of hydrochloric acid in isopropanol. The thus obtained precipitate is recovered by filtration and crystallized from 95% ethanol (70 ml) yielding 2.5 g of N-(1,2,3,4-tetrahydronaphth-1-yl)-2-hydroxy-3-(1-naphthyloxy)propanamine hydrochloride; m.p. 179°-183° C.

Reference： [1]Current Patent Assignee: SANOFI - US5254595, 1993, A

40
1-(2,6-diamino-4-pyrimidinyl)piperazine-bis-trifluoroacetate [ No CAS ]
conc. NH₄ OH [ No CAS ]
[ 2461-42-9 ]
1-[2-Hydroxy-3-(1-naphthyloxy)-propyl]-4-(2,6-diamino-4-pyrimidinyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.3%	With potassium carbonate In methanol; ethanol; ethyl acetate	20 1-[2-Hydroxy-3-(1-naphthyloxy)-propyl]-4-(2,6-diamino-4-pyrimidinyl)piperazine EXAMPLE 20 1-[2-Hydroxy-3-(1-naphthyloxy)-propyl]-4-(2,6-diamino-4-pyrimidinyl)piperazine A mixture of 1-(2,6-diamino-4-pyrimidinyl)piperazine-bis-trifluoroacetate (0.85 g, 2.0 mmol) and potassium carbonate (0.69 g, 5.0 mmol) in ethanol (60 ml) was stirred under reflux for 30 minutes. The mixture was filtered hot and to the filtrate a solution of 1,2-epoxy-3-(1-naphthyloxy)-propane (0.6 g, 3.0 mmol) in ethanol (10 ml) was added. The mixture was heated under reflux for 3 hours, the solvent was evaporated and the residue was partitioned between ethyl acetate (80 ml) and water (80 ml). The aqueous layer was separated and extracted with ethyl acetate (40 ml). The combined organic extracts were washed once with brine, dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column eluding with a 75:20:5 mixture of ethyl acetate, methanol and conc. NH4 OH. In this manner 0.58 g of the title compound was obtained as a foam, yield: 74.3%. Mp. after trituration with isopropyl ether: 122°-124° C.

Reference： [1]Current Patent Assignee: NISSHIN SEIFUN GROUP INC - US5380724, 1995, A

41
aqueous sodium chloride [ No CAS ]
[ 90-15-3 ]
[ 106-89-8 ]
[ 2461-42-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; tetra(n-butyl)ammonium hydrogen sulfate In water; toluene	1 [(1-naphthalenyloxy)methyl]oxirane STR8 EXAMPLE 1 [(1-naphthalenyloxy)methyl]oxirane STR8 28 9 Kg (309 moles) of chloromethyloxirane, 39 L of a 33% w/v solution of sodium hydroxide in water, 32 L of toluene and 0.9 Kg of tetrabutylammonium hydrogen sulfate are poured in a stainless steel reactor. 9 Kg (61.B moles) of 1-naphthol are added under efficient agitation in 45 min. minimum. The temperature is kept under 25° C. The agitation is maintained until reaction completion (about 20 hours). The aqueous layer is discarded and the organic phase extracted by 18 L of water and then with 18 L of an aqueous sodium chloride solution (5.5% w/v). The organic layer is concentrated under reduced pressure to yield 11.6 Kg of crude product. The crude product is used in the next reaction step. Yield: 92.8% from 1-naphthol.

Reference： [1]Current Patent Assignee: PFIZER INC - US4992535, 1991, A

42
[ 2461-42-9 ]
(+/-)1-amino-3-(1-naphthalenyloxy)-propanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; acetic acid In methanol; dichloromethane; water; ethyl acetate; toluene	2 (+-)1-amino-3-(1-naphthalenyloxy)-propanol STR9 EXAMPLE 2 (+-)1-amino-3-(1-naphthalenyloxy)-propanol STR9 116 L Of methanol are cooled to about 10° C. and saturated with gaseous ammonia (11.2 Kg), then 1.2 Kg of gaseous ammonia are additionally condensed at room temperature. 11.34 Kg of the product of Example 1 are dissolved in 6 L of methanol and added to the ammonia solution (T≤30° C.). After completion of addition, the reaction mixture is once again saturated with gaseous ammonia (2.8 Kg) at the same temperature. The reaction mixture is stirred overnight. The excess of ammonia is eliminated under reduced pressure (P=350 mbar at about 30° C.). The methanol is distilled under reduced pressure (P=20 mbar at about 40° C.). The residue is dissolved in 12 L of dichloromethane, then 39 L of water and 11 L of acetic acid are added. The mixture is stirred for about 30 min. and decanted. The aqueous layer is extracted twice with 6 L of dichloromethane. 33 L of toluene and 18 L of aqueous sodium hydroxide solution (30% w/v) are added to the aqueous layer. The reaction mixture is heated to T<70° C. and stirring is continued for about 1 hour. At this temperature the aqueous layer discarded and the organic layer re extracted twice with hot water. The remaining organic phase is concentrated under reduced pressure and the residue dissolved in 16 L of ethyl acetate at the reflux temperature. The product is crystallized (0° C≤T≤5° C.), filtered, washed with ethyl acetate and dried under reduced pressure at about 50° C. to afford 4.86 Kg of crude product. Yield: 39.6%.

Reference： [1]Current Patent Assignee: PFIZER INC - US4992535, 1991, A

43
[ 2461-42-9 ]
[ 14691-88-4 ]
[ 56490-29-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With calcium(II) trifluoromethanesulfonate In 1,4-dioxane at 140℃; for 0.333333h; Microwave irradiation;

Reference： [1]Location in patent: body text Hafner, Anja; Hrast, Martina; Pečar, Slavko; Mravljak, Janez [Tetrahedron Letters, 2009, vol. 50, # 5, p. 564 - 566]

44
[ 2461-42-9 ]
[ 77-71-4 ]
[ 301160-88-3 ]

Yield	Reaction Conditions	Operation in experiment
0.39 g	With pyridine In ethanol at 78℃; for 4h;	General procedure for reaction of epoxides with substituted 5,5-hydantoins, compounds 1 and 6-17 A stirred solution of epoxide (1 eq) the requisite 5,5-hydantoin (1 eq), in ethanol and catalytic pyridine was heated at reflux (78°C) for 4 hours. The reaction mixture was concentrated in vacuo.

Reference： [1]Fullam, Elizabeth; Abuhammad, Areej; Wilson, David L.; Anderton, Matthew C.; Davies, Steve G.; Russell, Angela J.; Sim, Edith [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 4, p. 1185 - 1190]

45
[ 2461-42-9 ]
[ 26907-54-0 ]
[ 1299492-03-7 ]

Reference： [1]Journal of the Chinese Chemical Society,2010,vol. 57,p. 1327 - 1330

46
[ 2461-42-9 ]
[ 90-15-3 ]
[ 17216-10-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With tetrabutylammomium bromide In toluene	1.2 Synthesis of 1,3-bis(1-naphthoxy)-2-propanol using 1-naphthyl glycidyl ether Example 1-(2) Synthesis of 1,3-bis(1-naphthoxy)-2-propanol using 1-naphthyl glycidyl ether 1-Naphthyl glycidyl ether (1.0 g, 5.0 mmol), as a starting material, was stirred with tetrabutylammonium bromide (0.322 g, 1 mmol) and 1-naphthol (0.865 g, 6 mmol) in a 50 mL round-bottom flask. Then, reaction was carried out at 110° C. for 4 hours and 30 minutes in a toluene solvent (20 mL) under reflux. The resulting crude product was purified by silica gel column chromatography (Rf=0.15, hexane:ethyl acetate=9:1, v/v). 1,3-Bis(1-naphthoxy)-2-propanol (1.55 g, 90%) was yielded. 1H NMR (CDCl3): δ 8.27 (m, 2H, Hs at ArH), 7.82 (m, 2H, Hs at ArH), 7.49 (m, 6H, Hs at ArH), 7.38 (t, J=7.2 Hz, 2H, Hs at ArH), 6.90 (d, J=7.2 Hz, 2H, Hs at ArH), 4.73 (m, 1H, H at C-2), 4.46 (m, 4H, Hs at C-1), 2.74 (d, J=5.4 Hz, 1H, Hs at OH).
83%	With tetrabutylammomium bromide; potassium carbonate; palladium dichloride In water at 60℃; for 4.5h;
72%	With tetrabutyl ammonium fluoride; silver nitrate In isopropyl alcohol at 60 - 80℃; for 8h; regioselective reaction;	4 The AgNP-catalysed epoxide phenolysis General procedure: Typical procedure for epoxide phenolysis catalysedby the in situ generated AgNPs iniPrOH (Table 2, entry 2): Themixture of TBAF (0.487 g, 2 mmol, 1 equiv) and AgNO3 0.01 mmol, 0.5 mol%) iniPrOH (4 mL) was stirred magneticallyunder reflux (oil bath temp 80C) for 15 min. The oil-bath tem-perature was reduced to 60C followed by addition of 6a (0.369 g,2 mmol) and 7a (0.248 g, 2 mmol) and the mixture was furtherstirred magnetically at 60C until completion of the reaction (6 h,TLC). The reaction mixture was cooled to rt and theiPrOH wasremoved under reduced pressure (30 mm Hg). The mixture wasdiluted with H2O (10 mL) and extracted with EtOAc (3 × 5 mL).The EtOAc layer was separated from the aqueous layer, dried (anhNa2SO4); filtered off and evaporated to dryness under vacuum(30 mm Hg). The residue was subjected to column chromatog-raphy (60-120 mesh silica-gel; 93:7 hexane-EtOAc as eluent) toafford the 8a as off white solid (0.463 g, 75%).

Reference： [1]Current Patent Assignee: HANYANG UNIVERSITY - US2012/10315, 2012, A1
[2]Seth, Kapileswar; Roy, Sudipta Raha; Pipaliya, Bhavin V.; Chakraborti, Asit K. [Chemical Communications, 2013, vol. 49, # 52, p. 5886 - 5888]
[3]Seth, Kapileswar; Roy, Sudipta Raha; Kommi, Damodara N.; Pipaliya, Bhavin V.; Chakraborti, Asit K. [Journal of Molecular Catalysis A: Chemical, 2014, vol. 392, p. 164 - 172]

47
[ 109-01-3 ]
[ 2461-42-9 ]
[ 34239-69-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	In methanol at 50℃;	5.2. General procedure for synthesis of β-amino alcohols 12-14 General procedure: The respective amine (1.1 equiv) was added to 1 equiv of the respective epoxide in MeOH (1 ml per 0.06 mmol starting material). The mixture was stirred at 50 °C, for 12-24 h, until the reaction was complete (verified via TLC). The excess solvent was removed under reduced pressure and the resulting oil purified using either preparative TLC or column chromatography.
61%	In ethanol for 1h; Reflux;	4 1-(4-methylpiperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1008) Example 4 1-(4-methylpiperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1008) To a solution of 2-((1-naphthyloxy)methyl)oxirane (50 mg, 0.25 mmol) in ethanol (0.50 mL) was added 4-methylpiperazine (33 μL, 0.30 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1008 (46 mg, 61%). 1H-NMR (400 MHz, acetone-d6) δ 2.18 (s, 3H), 2.30-2.45 (m, 1H), 2.50-2.65 (m, 1H), 2.59 (dd, J=12.4 and 6.9 Hz, 1H), 2.66 (dd, J=12.4 and 5.0 Hz, 1H), 2.80-3.00 (m, 6H), 4.15 (dd, J=10.5 and 6.8 Hz, 1H), 4.22-4.28 (m, 2H), 6.97 (d, J=7.8 Hz, 1H), 7.40 (t, J=8.2 Hz, 1H), 7.45-7.51 (m, 3H), 7.84 (d, J=7.8 Hz, 1H), 8.26-8.28 (d, J=7.8 Hz, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C18H25N2O2 ([M+H+]): 301.1911. Found 301.1929.
61%	In ethanol at 20℃; for 1h;	4 Example 4: 1-(4-methylpiperazinyl)-3-(1-naphthyloxy)propan-2-ol (HUHS 1008) 2-((1-naphthyloxy)methyl) (50 mg, 0.25 mmol) in ethanol (0.50 ml) solution of 4 - methylpiperazine (33 μL, 0.30 mmol) of the apparatus is at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (46 mg, 61%) was obtained by silica gel column chromatography of the crude product was purified HUHS1008.

Reference： [1]Location in patent: experimental part Tacon, Claire; Guantai, Eric M.; Smith, Peter J.; Chibale, Kelly [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 2, p. 893 - 902]
[2]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0200-0202
[3]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0085-0087

48
[ 2461-42-9 ]
[ 41202-32-8 ]
[ 112551-82-3 ]

Yield	Reaction Conditions	Operation in experiment
55%		General procedure: The respective amine (1.1 equiv) was added to 1 equiv of the respective epoxide in MeOH (1 ml per 0.06 mmol starting material). The mixture was stirred at 50 C, for 12-24 h, until the reaction was complete (verified via TLC). The excess solvent was removed under reduced pressure and the resulting oil purified using either preparative TLC or column chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 893 - 902

49
[ 2461-42-9 ]
[ 100-46-9 ]
1-benzylamino-3-(naphth-1-yloxy)-2-propanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	In methanol at 50℃;	5.2. General procedure for synthesis of β-amino alcohols 12-14 General procedure: The respective amine (1.1 equiv) was added to 1 equiv of the respective epoxide in MeOH (1 ml per 0.06 mmol starting material). The mixture was stirred at 50 °C, for 12-24 h, until the reaction was complete (verified via TLC). The excess solvent was removed under reduced pressure and the resulting oil purified using either preparative TLC or column chromatography.

Reference： [1]Location in patent: experimental part Tacon, Claire; Guantai, Eric M.; Smith, Peter J.; Chibale, Kelly [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 2, p. 893 - 902]

50
[ 35161-71-8 ]
[ 2461-42-9 ]
[ 1453205-13-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With calcium(II) trifluoromethanesulfonate In acetone at 100℃; for 0.166667h; Microwave irradiation; Sealed tube;

Reference： [1]Schmitt, Martin L.; Hauser, Alexander-Thomas; Carlino, Luca; Pippel, Martin; Schulz-Fincke, Johannes; Metzger, Eric; Willmann, Dominica; Yiu, Teresa; Barton, Michelle; Schüle, Roland; Sippl, Wolfgang; Jung, Manfred [Journal of Medicinal Chemistry, 2013, vol. 56, # 18, p. 7334 - 7342]

51
[ 2461-42-9 ]
[ 1836-62-0 ]
[ 1479050-16-2 ]

Yield	Reaction Conditions	Operation in experiment
86%	In isopropyl alcohol; for 5h;Inert atmosphere; Reflux;	General procedure: Corresponding 2-(aryloxymethyl)oxiranes (5 mmol, 1 equiv) and amines (7.5 mmol, 1.5 equiv) were dissolved in 30 mL i-PrOH. The reaction was purged with argon 3 times and stirred at reflux for 5 h, andthen the mixture was cooled to room temperature and added AcOEt.After washing with brine 3 times, the organic layer was dried overanhydrous Na2SO4, filtered, and evaporated in vacuo. Purification ofthe crude residue by column chromatography on silica gel yielded target compounds.

Reference： [1]Bioorganic and medicinal chemistry,2020,vol. 28
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 8626 - 8655

52
[ 2461-42-9 ]
[ 99-76-3 ]
methyl 4-(2-hydroxy-3-(naphthalen-1-yloxy)propoxy)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69.6%	Stage #1: methyl 4-hydroxylbenzoate With methanol; potassium hydroxide at 20℃; Stage #2: 3-(1-naphthyloxy)-1,2-epoxypropane With tetrabutylammomium bromide In N,N-dimethyl-formamide; toluene at 120℃; for 20h;

Reference： [1]Tomašić, Tihomir; Rabbani, Said; Gobec, Martina; Raščan, Irena Mlinarič; Podlipnik, Črtomir; Ernst, Beat; Anderluh, Marko [MedChemComm, 2014, vol. 5, # 8, p. 1247 - 1253]

53
[ 2461-42-9 ]
[ 14199-15-6 ]
methyl 2-(4-(2-hydroxy-3-(naphthalen-1-yloxy)propoxy)phenyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.1%	Stage #1: Methyl 4-hydroxyphenylacetate With methanol; potassium hydroxide at 20℃; Stage #2: 3-(1-naphthyloxy)-1,2-epoxypropane With tetrabutylammomium bromide In N,N-dimethyl-formamide; toluene at 90℃; for 2h;

Reference： [1]Tomašić, Tihomir; Rabbani, Said; Gobec, Martina; Raščan, Irena Mlinarič; Podlipnik, Črtomir; Ernst, Beat; Anderluh, Marko [MedChemComm, 2014, vol. 5, # 8, p. 1247 - 1253]

54
[ 2461-42-9 ]
[ 75-31-0 ]
[ 4199-09-1 ]

Yield	Reaction Conditions	Operation in experiment
90 % ee	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane With L-Tartaric acid; O₄₀PW₁₂^(3-)2.5Cs⁽¹⁺⁾0.5H⁽¹⁺⁾ In ethanol for 0.25h; Green chemistry; Stage #2: isopropylamine In ethanol for 24h; Reflux; Green chemistry; enantioselective reaction;	Synthesis of (S)-(-)-Propranolol (4) A solution of glycidyl-a-naphthyl ether 3 (8 mmol, 1.6 g), L-(+)-tartaric acid (8 mmol, 1.2 g) and nanoparticlesCs2.5H0.5PW12O40 catalyst (0.03 g) in (20 mL) ethanol wasstirred for 15 min. The isopropylamine (16 mmol, 1.2 mL)was added and stirred and to reflux for 24 h The reactionmixture was cooled and filtered. The solid was washed withdichloromethane and then treated with aqueous 10% sodiumhydroxide solution (10 mL), and extracted with dichloromethane(2 £ 50 mL). The combined organic layer was washedwith water (5 £ 50 mL) and dried over sodium sulfate. Thesolvent was removed under reduced pressure to give crudeproduct (1.59 g, 77% yield), that showed 90% ee for (S)-(-)-propranolol. mp D 72C [a] D -9.08 (C D 1.0, EtOH),[a]D D -10.2 (C D 1.02 EtOH).19

Reference： [1]Gharib, Ali; Jahangir, Manouchehr; Roshani, Mina; Pesyan, Nader Noroozi; Scheeren; Mohadesazadeh, Sara; Lagzian, Shirin [Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 2015, vol. 45, # 3, p. 350 - 355]

55
[ 2461-42-9 ]
[ 124-38-9 ]
4-((naphthalen-1-yloxy)methyl)-1,3-dioxolan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.8%	With tetrabutylammomium bromide; Mo₂(O-t-Bu)6 In dichloromethane at 25℃; for 24h; Schlenk technique;
89%	With tetra-(n-butyl)ammonium iodide; 3-ethoxy-1,1,1,2,3,4,4,5,5,6,6,6-dodecafluoro-2-(trifluoromethyl)hexane at 80℃; for 6h; Autoclave;
82%	With imidazolium based ionic liquid incorporated porous dendritic fibrous nanosilica at 70℃; for 2h; Green chemistry;	2.5 General Procedures forPreparation ofCyclicCarbonate General procedure: IL/DFNS NPs (5mg) and epoxide derivatives (1mmol) werecharged into the reactor vessel without using any co-solvent. The reactor vessel was placed under a constant pressure ofcarbon dioxide and then heated to 70°C for 2h. Then thereactor was cooled to ambient temperature, and the resultingmixture was transferred to a 50mL round bottom flask.Upon completion, the progress of the reaction was monitoredby TLC when the reaction was completed, EtOH wasadded to the reaction mixture and the KCC-1/IL/HPW NPswas separated by filteration. Then the solvent was removedfrom solution under reduced pressure and the resulting productpurifed by recrystallization using n-hexane/ethyl acetate.

81%	With C₂₂H₂₄F₆N₃O⁽¹⁺⁾*Br^(1-) In neat (no solvent) at 80℃; for 24h;
	With 2Zn⁽²⁺⁾C₁₃H₂₀N₆2C₁₂H₆O₄^(2-); tetrabutylammomium bromide at 80℃; for 4h; Sealed tube;
	With tetrabutylammomium bromide at 100℃; Autoclave;
14 %Chromat.	With tetrabutylammomium bromide; 2C₂₆H₁₆N₂O₈^(2-)2Mn⁽²⁺⁾3H₂O In neat (no solvent) at 70℃; for 48h; Schlenk technique;

Reference： [1]Chen, Jing-Huo; Deng, Cheng-Hua; Fang, Sheng; Ma, Jian-Gong; Cheng, Peng [Green Chemistry, 2018, vol. 20, # 5, p. 989 - 996]
[2]Mamone, Marius; Milcent, Thierry; Crousse, Benoit [Chemical Communications, 2015, vol. 51, # 64, p. 12736 - 12739]
[3]Zhang, Pu; Zhiani, Rahele [Catalysis Letters, 2020, vol. 150, # 8, p. 2254 - 2266]
[4]Li, Yue-Dan; Cui, Dong-Xiao; Zhu, Jun-Chao; Huang, Ping; Tian, Zhuang; Jia, Yan-Yan; Wang, Ping-An [Green Chemistry, 2019, vol. 21, # 19, p. 5231 - 5237]
[5]Zhao, Dan; Liu, Xiao-Hui; Guo, Jin-Han; Xu, Hua-Jin; Zhao, Yue; Lu, Yi; Sun, Wei-Yin [Inorganic Chemistry, 2018, vol. 57, # 5, p. 2695 - 2704]
[6]Li, He; Feng, Xiao; Shao, Pengpeng; Chen, Jian; Li, Chunzhi; Jayakumar, Sanjeevi; Yang, Qihua [Journal of Materials Chemistry A, 2019, vol. 7, # 10, p. 5482 - 5492]
[7]Lin, Haonan; Deng, Cheng-Hua; Qiu, Xiaohang; Liu, Xiao; Ma, Jian-Gong; Cheng, Peng [Crystal Growth and Design, 2021, vol. 21, # 7, p. 3728 - 3735]

56
[ 2461-42-9 ]
[ 13754-38-6 ]
3-(1-naphthyloxy)-1-(4-(phenylcarbonyl)piperazinyl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	In ethanol for 1h; Reflux;	8 3-(1-naphthyloxy)-1-(4-(phenylcarbonyl)piperazinyl)propan-2-ol (HUHS1012) Example 8 3-(1-naphthyloxy)-1-(4-(phenylcarbonyl)piperazinyl)propan-2-ol (HUHS1012) To a solution of 2-((1-naphthyloxy)methyl)oxirane (50 mg, 0.25 mmol) in ethanol (0.50 mL) was added 4-(phenylcarbonyl)piperazine (57 mg, 0.30 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1012 (58 mg, 59%). 1H-NMR (400 MHz, CDCl3) δ 2.48-2.81 (m, 6H), 3.49 (br s, 2H), 3.86 (br s, 2H), 4.14-4.18 (dd, J=10.5 and 5.0 Hz, 1H), 4.22 (dd, J=10.5 and 5.0 Hz 1H), 4.27-4.32 (m, 1H), 6.83 (d, J=7.3 Hz, 1H), 7.37 (t, J=7.8 Hz, 1H), 7.40-7.52 (m, 8H), 7.80-7.82 (m, 1H), 8.22-8.25 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C24H27N2O3 ([M+H+]): 391.2016. Found 391.2022.
59%	In ethanol at 20℃; for 1h;	8 Example 8: 3-(1-naphthyloxy)-1-(4-(phenylcarbonyl)piperazinyl)propan-2-ol (HUHS 1012) 2-((1-naphthyloxy)methyl) (50 mg, 0.25 mmol) 4 - (phenylcarbonyl) piperazine (0.50 ml) of the ethanol solution of oxirane (57 mg, 0.30 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (58 mg, 59%) was obtained by silica gel column chromatography of the crude product was purified HUHS1012

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0212-0214
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0097-0099

57
[ 58333-75-8 ]
[ 2461-42-9 ]
1-(4-(2-methoxyphenyl)piperidin-1-yl)-3-(1-naphthyloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	In ethanol; for 1h;Reflux;	Example 13 1-(4-(2-methoxyphenyl)piperidin-1-yl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1017) To a solution of 2-((1-naphthyloxy)methyl)oxirane (100 mg, 0.50 mmol) in ethanol (1 mL) was added <strong>[58333-75-8]4-(2-methoxyphenyl)piperidine</strong> (116 mg, 0.60 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1017 (76 mg, 39%). 1H-NMR (400 MHz, CDCl3) delta 1.75-1.78 (m, 4H), 2.27 (dt, J=11.7 and 2.8 Hz, 1H), 2.49-2.58 (m, 1H), 2.74 (d, J=6.9 Hz, 2H), 2.98-3.07 (m, 2H), 3.24 (d, J=11.5 Hz, 1H), 3.84 (s, 3H), 4.15 (dd, J=9.6 and 5.0 Hz, 1H), 4.25 (dd, J=9.6 and 5.0 Hz, 1H), 4.30-4.36 (m, 1H), 6.85 (t, J=7.8 Hz, 2H), 6.95 (dt, J=7.4 and 0.92 Hz, 1H), 7.18-7.23 (m, 2H), 7.37 (t, J=7.8 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.45-7.52 (m, 2H), 7.78-7.82 (m, 1H), 8.25-8.28 (m, 1H); ESI-HRMS (positive ion, sodium formate). calcd. for C25H30NO3 ([M+H+]): 392.2220. Found 392.2249.
39%	In ethanol; for 1h;Reflux;	2-((1-naphthyloxy)methyl)-<strong>[58333-75-8]4-(2-methoxyphenyl)piperidine</strong> (100 mg, 0.50 mmol) in ethanol (1 ml) solution of oxirane (116 mg, 0.60 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (76 mg, 39%) was obtained by silica gel column chromatography of the crude product was purified HUHS1017.

Reference： [1]Patent: US2015/353473,2015,A1 .Location in patent: Paragraph 0227-0229
[2]Patent: JP6041303,2016,B2 .Location in patent: Paragraph 0112-0114

58
[ 54256-45-0 ]
[ 2461-42-9 ]
3-(1-naphthyloxy)-1-(4-octylpiperazinyl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In ethanol for 1h; Reflux;	15 3-(1-naphthyloxy)-1-(4-octylpiperazinyl)propan-2-ol (HUHS1019) Example 15 3-(1-naphthyloxy)-1-(4-octylpiperazinyl)propan-2-ol (HUHS1019) To a solution of 2-((1-naphthyloxy)methyl)oxirane (10 mg, 0.50 mmol) in ethanol (1 mL) was added 4-octylpiperazine (119 mg, 0.64 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1019 (155 mg, 85%). 1H-NMR (400 MHz, CDCl3) δ 0.88 (t, J=7.6 Hz, 3H), 1.20-1.40 (m, 10H), 1.44-1.57 (m, 2H), 2.30-2.35 (m, 2H), 2.35-2.60 (m, 4H), 2.60-2.70 (m, 4H), 2.75-2.85 (m, 2H), 4.15 (dd, J=10.5 and 5.0 Hz, 1H), 4.20 (dd, J=10.5 and 5.0 Hz, 1H), 4.22-4.32 (m, 1H), 6.82 (d, J=7.2 Hz, 1H), 7.38 (t, J=7.3 Hz, 1H), 7.45 (d, J=8.2 Hz, 1H), 7.45-7.55 (m, 2H), 7.84-7.86 (m, 1H), 8.23-8.35 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C25H38N2O2 ([M+H+]): 399.3006. Found 399.3024.
85%	In ethanol at 20℃; for 1h;	15 Example 15: 3-(1-naphthyloxy)-1-(4-octylpiperazinyl)propan-2-ol (HUHS 1019) 2-((1-naphthyloxy)methyl) (10 mg, 0.50 mmol) in ethanol (1 ml) (119 mg, 0.64 mmol) 4 - solution of oxirane octyl piperazine was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (155 mg, 85%) was obtained by silica gel column chromatography of the crude product was purified HUHS1019.

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0233-0235
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0118-0120

59
[ 2461-42-9 ]
[ 57536-86-4 ]
3-(1-naphthyloxy)-1-(4-(1-naphthyl)piperazinyl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	In ethanol for 1h; Reflux;	16 3-(1-naphthyloxy)-1-(4-(1-naphthyl)piperazinyl)propan-2-ol (HUHS1020) Example 16 3-(1-naphthyloxy)-1-(4-(1-naphthyl)piperazinyl)propan-2-ol (HUHS1020) To a solution of 2-((1-naphthyloxy)methyl)oxirane (55 mg, 0.27 mmol) in ethanol (1 mL) was added 4-(1-naphthyl)piperazine (70 mg, 0.33 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1020 (28 mg, 25%). 1H-NMR (400 MHz, CDCl3) 52.78-2.75 (m, 4H), 3.00-3.25 (m, 6H), 4.19 (dd, J=9.6 and 5.0 Hz, 1H), 4.28 (dd, J=9.6 and 5.0 Hz, 1H), 4.32-4.38 (m, 1H), 6.86 (d, J=7.2 Hz, 1H), 7.11 (dd, J=7.3 and 0.92 Hz, 1H), 7.37-7.58 (m, 9H), 7.80-7.84 (m, 2H), 8.19-8.22 (m, 1H), 8.28-8.30 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C27H29N2O2 ([M+H+]): 413.2224. Found 413.2222.
25%	In ethanol at 20℃; for 1h;	16 Example 16: 3-(1-naphthyloxy)-1-(4-(1-naphthyl)piperazinyl)propan-2-ol (HUHS 1020) 2-((1-naphthyloxy)methyl)-4-(1-naphthyl) piperazine (55 mg, 0.27 mmol) in ethanol (1 ml) solution of oxirane (70 mg, 0.33 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (28 mg, 25%) was obtained by silica gel column chromatography of the crude product was purified HUHS1020.

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0236-0238
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0121-0123

60
[ 2461-42-9 ]
[ 57536-91-1 ]
3-(1-naphthyloxy)-1-(4-(2-naphthyl)piperazinyl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	In ethanol for 1h; Reflux;	17 3-(1-naphthyloxy)-1-(4-(2-naphthyl)piperazinyl)propan-2-ol (HUHS1021) Example 17 3-(1-naphthyloxy)-1-(4-(2-naphthyl)piperazinyl)propan-2-ol (HUHS1021) To a solution of 2-((1-naphthyloxy)methyl)oxirane (50 mg, 0.25 mmol) in ethanol (1 mL) was added 4-(2-naphthyl)piperazine (64 mg, 0.30 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1021 (39 mg, 38%). 1H-NMR (400 MHz, CDCl3) δ 2.71-2.82 (m, 4H), 2.92-2.97 (m, 2H), 3.320-3.40 (m, 4H), 4.19 (dd, J=9.6 and 5.0 Hz, 1H), 4.27 (dd, J=9.6 and 5.0 Hz, 1H), 4.31-4.37 (m, 1H), 6.86 (d, J=7.3 Hz, 1H), 7.14 (d, J=2.3 Hz, 1H), 7.26-7.53 (m, 7H), 7.69-7.75 (m, 3H), 7.80-7.83 (m, 1H), 8.26-8.29 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C27H29N2O2 ([M+H+]): 413.2224. Found 413.2222.
38%	In ethanol at 20℃; for 1h;	17 Example 17: 3-(1-naphthyloxy)-1-(4-(2-naphthyl)piperazinyl)propan-2-ol (HUHS 1021) 2-((1-naphthyloxy)methyl)-4-(2-naphthyl)piperazine (50 mg, 0.25 mmol) in ethanol (1 ml) solution of oxirane (64 mg, 0.30 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (39 mg, 38%) was obtained by silica gel column chromatography of the crude product was purified HUHS1021.

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0239-0241
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0124-0126

61
[ 2461-42-9 ]
[ 1539-42-0 ]
C₂₅H₂₅N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	at 20℃; for 120h;	2.8.1. Synthesis of HL1 Ligand HL1 (Scheme 1) was prepared by the reaction between bis-(pyridin-2-ylmethyl)amine [31] (0.025 mol, 4.98 g) and 2-(1-naphthylmethyl)oxirane (0.025 mol, 5 g), in ethanol. The mixture was stirred for 5 days at room temperature, which was follow by TLC, using ethanol as eluent. Subsequently, the solvent was removed under reduced pressure and the residue was to 50 cm3 of water. The compound was extracted with five 50 cm3 portion of CHCl3 and the extracts were combined, washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. A brown oil was obtained. Yield: 6.5 g (65%). 1H NMR (400 MHz, CDCl3) δ/ppm: 2.96(dd, 1H), 3.12 (dd, 1H), 3.97 (d, 2H), 4.05-4.09 (m, 3H), 4.19 (dd, 1H),4.28-4.35 (m, 1H), 6.77 (d, 1H), 7.12-7.16 (m, 4H), 7.32-7.36 (m. 1H),7.39 (dd, 1H), 7.46 (t, 2H), 7.58 (t, 2H), 7.76 (d, 1H), 8.09 (d, 1H), and 8.56 (m, 2H). 13C NMR (100 MHz, CDCl3) δ/ppm: 58.20, 60.78 (2C),67.99, 70.27, 104.87, 120.50, 122.26, 122.42 (2C), 123.43 (2C), 125.26,125.78, 126.07, 126.29, 127.59, 134.64, 136.88 (2C), 149.21 (2C),154.65, and 157.28(2C). IR (cm-1) ν: 3700-3100, 3051, 2928,2839, 1628, 1589, 1508, 1435, 1269, 791, 771. UV-Vis λ(nm) data(ε, dm3 mol-1 cm-1): 210 (7.39 × 104), 230 (4.79 × 104), 262(1.29 × 104), 267 (1.24 × 104), 292 (9.64 × 103), 305 (6.35 × 103),and 320 (3.7 × 103).

Reference： [1]Fernandes, Christiane; Horn, Adolfo; Lopes, Bruna F.; Bull, Erika S.; Azeredo, Nathália F.B.; Kanashiro, Milton M.; Borges, Franz V.; Bortoluzzi, Adailton J.; Szpoganicz, Bruno; Pires, Anderson B.; Franco, Roberto W.A.; Almeida, João Carlos De A.; Maciel, Leide L.F.; Resende, Jackson A.L.C.; Schenk, Gerhard [Journal of Inorganic Biochemistry, 2015, vol. 153, p. 68 - 87]

62
[ 2461-42-9 ]
[ 63671-68-1 ]
2-[[2-hydroxy-3-(1-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	at 20℃; for 24h;	2.8.1. Synthesis of HL1 General procedure: Ligand HL1 (Scheme 1) was prepared by the reaction between bis-(pyridin-2-ylmethyl)amine [31] (0.025 mol, 4.98 g) and 2-(1-naphthylmethyl)oxirane (0.025 mol, 5 g), in ethanol. The mixture was stirred for 5 days at room temperature, which was follow by TLC, using ethanol as eluent. Subsequently, the solvent was removed under reduced pressure and the residue was to 50 cm3 of water. The compound was extracted with five 50 cm3 portion of CHCl3 and the extracts were combined, washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. A brown oil was obtained. Yield: 6.5 g (65%).

Reference： [1]Fernandes, Christiane; Horn, Adolfo; Lopes, Bruna F.; Bull, Erika S.; Azeredo, Nathália F.B.; Kanashiro, Milton M.; Borges, Franz V.; Bortoluzzi, Adailton J.; Szpoganicz, Bruno; Pires, Anderson B.; Franco, Roberto W.A.; Almeida, João Carlos De A.; Maciel, Leide L.F.; Resende, Jackson A.L.C.; Schenk, Gerhard [Journal of Inorganic Biochemistry, 2015, vol. 153, p. 68 - 87]

63
[ 2461-42-9 ]
[ 19438-10-9 ]
methyl 3-(2-hydroxy-3-(naphthalen-1-yloxy)propoxy)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43.4%	Stage #1: methyl 3-hydroxybenzoate With potassium hydroxide In methanol at 20℃; for 0.333333h; Stage #2: 3-(1-naphthyloxy)-1,2-epoxypropane With tetrabutylammomium bromide In methanol; N,N-dimethyl-formamide; toluene at 90℃;

Reference： [1]Kotar, Anita; Tomašič, Tihomir; Lenarčič Živković, Martina; Jug, Gregor; Plavec, Janez; Anderluh, Marko [Organic and Biomolecular Chemistry, 2016, vol. 14, # 3, p. 862 - 875]

64
[ 2461-42-9 ]
1-(3-ammoniopropyl)-4-methylquinolinium dibromide [ No CAS ]
1-(3-(2-hydroxy-3-(naphthalen-1-yloxy)propylamino)propyl)-4-methylquinolinium bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In water at 20℃; for 24h;	3.c (c) Preparation of 1-(3-(2-hydroxy-3-(naphthalen-1-yloxy)propylamino)propyl)-4-methylquinolinium bromide (Compound 3) (c) Preparation of 1-(3-(2-hydroxy-3-(naphthalen-1-yloxy)propylamino)propyl)-4-methylquinolinium bromide (Compound 3) To a suspension of Compound 1 (0.17 g, 0.83 mmol) and Compound 2 (0.30 g, 0.83 mmol) in water (1 mL), triethylamine (0.10 g, 0.99 mmol) was added. The combined mixture was stirred at room temperature for 24 hours and then evaporated in the rotary evaporator to provide Compound 3 as a solid. This product was used without any workup and further purification. The structure of Compound 3 is given below:

Reference： [1]Current Patent Assignee: ENZO BIOCHEM INC - US9250249, 2016, B2 Location in patent: Page/Page column 59; 60

65
[ 2461-42-9 ]
N<SUP>1</SUP>-(acridin-9-yl)ethane-1,2-diamine hydrochloride [ No CAS ]
C₂₈H₂₇N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8%	With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 50℃; for 20h;	5.b (b) Preparation of Dye 5 To a solution of Compound 1 (200 mg, 1 mmol) in diisopropylethylamine (0.6 mL) and dioxane (4 mL), was added Compound 7 (274 mg, 1 mmol). The reaction mixture was heated at 50° C. for 20 hrs. The yellow precipitate was collected by centrifugation and then further purified by flash chromatography (gradient of mobile phase: dichloromethane/methanol=50/1 to 5/1). The solvent was removed under vacuum to provide Dye 5 as a yellow solid (34.5 mg, 8%). Abs (max, methanol)=412 and 440 nm; Em (max, methanol)=426, 452 and 480 nm. The structure of Dye 5 is given below:

Reference： [1]Current Patent Assignee: ENZO BIOCHEM INC - US9250249, 2016, B2 Location in patent: Page/Page column 63; 64

66
[ 4318-42-7 ]
[ 2461-42-9 ]
1-(4-isopropylpiperazinyl)-3-(1-naphthyloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	In ethanol for 1h; Reflux;	5 1-(4-isopropylpiperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1009) Example 5 1-(4-isopropylpiperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1009) To a solution of 2-((1-naphthyloxy)methyl)oxirane (50 mg, 0.25 mmol) in ethanol (0.50 mL) was added 4-isopropylperazine (43 μL, 0.30 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1009 (56 mg, 68%). 1H-NMR (400 MHz, acetone-d6) δ 0.99 (d, J=7.3 Hz, 6H), 2.52-2.68 (m, 7H), 2.88-2.93 (m, 4H), 4.14-4.18 (m, 1H), 4.21-4.28 (m, 2H), 6.96 (d, J=7.4 Hz, 1H), 7.37-7.52 (m, 4H), 7.82-7.86 (m, 1H), 8.29-8.32 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C20H29N2O2 ([M+H+]): 329.2224. Found 329.2239.
68%	In ethanol at 20℃; for 1h;	5 Example 5: 1-(4-isopropylpiperazinyl)-3-(1-naphthyloxy)propan-2-ol (HUHS 1009) 2-((1-naphthyloxy) methyl) (50 mg, 0.25 mmol) in ethanol (0.50 ml) solution of 4 - (43 μL, 0.30 mmol) oxirane [...] was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (56 mg, 68%) was obtained by silica gel column chromatography of the crude product was purified HUHS1009.

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0203-0205
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0088-0090

67
[ 5610-49-1 ]
[ 2461-42-9 ]
3-(1-naphthyloxy)-1-(4-butylpiperazinyl)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	In ethanol for 1h; Reflux;	6 3-(1-naphthyloxy)-1-(4-propylpiperazinyl)propan-2-ol (HUHS1010) Example 6 3-(1-naphthyloxy)-1-(4-propylpiperazinyl)propan-2-ol (HUHS1010) To a solution of 2-((1-naphthyloxy)methyl)oxirane (50 mg, 0.25 mmol) in ethanol (0.50 mL) was added 4-propylpiperazine (44 μL, 0.30 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1010 (81 mg, 95%). 1H-NMR (400 MHz, acetone-d6) δ 0.90 (t, J=7.6 Hz, 3H), 1.28-1.57 (m, 2H), 1.40-1.47 (m, 2H), 2.28 (t, J=7.3 Hz, 2H), 2.56-2.69 (m, 6H), 3.05 (br s, 2H), 3.31 (s, 2H), 4.15 (dd, J=10.5 and 6.8 Hz, 1H), 4.22-4.28 (m, 2H), 6.97 (d, J=7.2 Hz, 1H), 7.40 (t, J=7.3 Hz, 1H), 7.45-7.51 (m, 3H), 7.85 (dd, J=8.2 and 0.92 Hz, 1H), 8.31 (dd, J=7.8 and 0.92 Hz, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C21H31N2O2 ([M+H+]): 343.2380. Found 343.2340.
95%	In ethanol at 20℃; for 1h;	6 Example 6: 3-(1-naphthyloxy)-1-(4-propylpiperazinyl)propan-2-ol (HUHS 1010) 2-((1-naphthyloxy)methyl) (50 mg, 0.25 mmol) in ethanol (0.50 ml) solution of 4 - (44 μL, 0.30 mmol) oxirane propyl piperazine was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (81 mg, 95%) was obtained by silica gel column chromatography of the crude product was purified HUHS1010.

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0206-0208
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0091-0093

68
[ 2461-42-9 ]
[ 36908-21-1 ]
1-((2-((2-methoxyphenyl)amino)ethyl)amino)-3-(1-naphthyloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.2%	In ethanol for 1h; Reflux;	11 1-((2-((2-methoxyphenyl)amino)ethyl)amino)-3-(1-naphthyloxy)propan-2-ol (HUHS1015) Example 11 1-((2-((2-methoxyphenyl)amino)ethyl)amino)-3-(1-naphthyloxy)propan-2-ol (HUHS1015) To a solution of 2-((1-naphthyloxy)methyl)oxirane (482 mg, 2.4 mmol) in ethanol (3 mL) was added 2-((2-methoxyphenyl)amino)ethyl)amine (200 mg, 1.2 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1015 (11 mg, 1.2%). 1H-NMR (400 MHz, CDCl3) δ 2.91-3.05 (m, 4H), 3.31 (t, J=6.0 Hz, 2H), 3.82 (s, 3H), 4.13-4.26 (m, 3H), 6.64-6.71 (m, 2H), 6.77 (d, J=7.8 Hz, 1H), 6.82 (d, J=7.8 Hz, 1H), 6.87 (t, J=7.8 Hz, 1H), 7.36 (dd, J=8.2 and 7.8 Hz, 1H), 7.43-7.50 (m, 3H), 7.80 (d, J=8.3 Hz, 1H), 8.23 (d, J=7.8 Hz, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C22H27N2O3 ([M+H+]): 367.2016. Found 367.2054.
1.2%	In ethanol for 1h; Reflux;	11 Example 11: 1-((2-((2-methoxyphenyl)amino)ethyl)amino)-3-(1-naphthyloxy) propan-2-ol (HUHS 1015) 2-((1-naphthyloxy)methyl) (482 mg, 2.4 mmol) in ethanol (3 ml) solution of 2-oxirane((2-methoxyphenyl)amino)ethyl) amine (200 mg, 1.2 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (11 mg, 1.2%) was obtained HUHS1015.

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0221-0223
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0106-0108

69
[ 2461-42-9 ]
[ 82502-77-0 ]
1-(4-heptylpiperazinyl)-3-(1-naphthyloxy)propane-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In ethanol for 1h; Reflux;	14 1-(4-heptylpiperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1018) Example 14 1-(4-heptylpiperazinyl)-3-(1-naphthyloxyl)propan-2-ol (HUHS1018) To a solution of 2-((1-naphthyloxy)methyl)oxirane (106 mg, 0.53 mmol) in ethanol (1 mL) was added 4-heptylpiperazine (118 mg, 0.64 mmol) at room temperature. The mixture was stirred under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to give HUHS1018 (188 mg, 93%). 1H-NMR (400 MHz, CDCl3) δ 0.88 (t, J=7.6 Hz, 3H), 1.20-1.40 (m, 8H), 1.44-1.57 (m, 2H), 2.30-2.35 (m, 2H), 2.35-2.60 (m, 4H), 2.60-2.70 (m, 4H), 2.75-2.85 (m, 2H), 4.15 (dd, J=10.5 and 5.0 Hz, 1H), 4.20 (dd, J=10.5 and 5.0 Hz, 1H), 4.22-4.32 (m, 1H), 6.82 (d, J=7.2 Hz, 1H), 7.38 (t, J=7.3 Hz, 1H), 7.45 (d, J=8.2 Hz, 1H), 7.45-7.55 (m, 2H), 7.84-7.86 (m, 1H), 8.23-8.35 (m, 1H); ESI-HRMS (positive ion, sodium formate) calcd. for C24H16N2O2 ([M+H+]): 385.2861. Found 385.2861.
93%	In ethanol at 20℃; for 1h;	14 Example 14: 1-(4-heptylpiperazinyl)-3-(1-naphthyloxy)propan-2-ol (HUHS 1018) 2-((1-naphthyloxy)methyl) (106 mg, 0.53 mmol) in ethanol (1 ml) (118 mg, 0.64 mmol) 4-solution of oxirane heptyl piperazine was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (188 mg, 93%) was obtained by silica gel column chromatography of the crude product was purified HUHS1018.

Reference： [1]Current Patent Assignee: NISHIZAKI BIOINFORMATION RESEARCH INSTITUTE - US2015/353473, 2015, A1 Location in patent: Paragraph 0230-0232
[2]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0115-0117

70
[ 2461-42-9 ]
[ 532-55-8 ]
1-(naphthalen-1-yloxy)-3-thiocyanatopropan-2-yl benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With 1-methyl-1H-imidazole In neat (no solvent) at 20℃; for 8h; regioselective reaction;

Reference： [1]Modi, Anju; Ali, Wajid; Patel, Bhisma K. [Organic Letters, 2017, vol. 19, # 3, p. 432 - 435]

71
[ 2461-42-9 ]
[ 107-11-9 ]
[ 4563-15-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane; 1-amino-2-propene In N,N-dimethyl-formamide at 60℃; for 12h; Sealed tube; Stage #2: With water In N,N-dimethyl-formamide at 60℃; for 12h; Sealed tube; regioselective reaction;	General method for synthesis of amino alcohols: General procedure: In a 20 mL pressure tube (for volatile amines) was combined epoxide (1.0 mmol, 1.0 equiv) and amine (1.5 mmol, 1.5 equiv) 6.7 mL of reagent grade DMF. The reaction vessel fitted with a stirbar, sealed, and heated at 60°C for 12 h after which the vessel was allowed to cool to ambient temperature (not necessary for reactions not ran in pressure vessels) before receiving deionized water (50 equiv) in one portion. The vessel was resealed and stirred at 60°C for an additional 12 h. Solvent was removed on a rotary evaporator (22.5 mbar at 35°C) and the crude residue loaded directly onto a silica gel column.

Reference： [1]Lizza, Joseph R.; Moura-Letts, Gustavo [Synthesis, 2017, vol. 49, # 6, p. 1231 - 1242]

72
[ 2461-42-9 ]
[ 35386-24-4 ]
1-(4-(2-methoxyphenyl)piperazinyl)-3-(2-naphthyloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	In ethanol at 20℃; for 1h;	4 Reference Example 4 1-(4-(2-methoxyphenyl) piperazinyl)-3-(2-naphthyloxy) propan-2-ol (HUHS 1005) 2-((2-naphthyloxy)methyl)-4-(2 methoxyphenyl) piperazine (75 mg, 0.38 mmol) in ethanol (0.75 ml) solution of oxirane (79 uL, 0.45 mmol) was added at room temperature. The mixture was stirred refluxing 1. The reaction mixture was concentrated under reduced pressure. (149 mg, 100%) was obtained by silica gel column chromatography of the crude product was purified HUHS1005.

Reference： [1]Current Patent Assignee: KTN BIOTECH - JP6041303, 2016, B2 Location in patent: Paragraph 0076-0078

73
[ 2461-42-9 ]
[ 13641-96-8 ]
[ 79-10-7 ]
C₂₂H₂₃NO₇ [ No CAS ]
C₂₂H₂₃NO₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-(1-naphthyloxy)-1,2-epoxypropane; acrylic acid With 2,6-di-tert-butyl-4-methyl-phenol; triphenylphosphine at 90℃; for 22.7h; Stage #2: acrylic acid 2-isocyanatoethyl ester With dibutyltin(II) dilaurate at 60℃; for 21.5h;	3.9 General Method for Preparation of the Inventive Aromatic Glycol Ether Writing Monomers (Examples 3.1-3.11) General procedure: General Method for Preparation of the Inventive Aromatic Glycol Ether Writing Monomers (Examples 3.1-3.11) (0252) The precursor (Example 2.1-2.11), dibutyltin dilaurate and 2,6-di-tert-butyl-4-methylphenol were initially charged in a three-neck flask which was equipped with a precision glass stirrer and stirrer motor, gas inlet and drying tube. Subsequently, the mixture was heated to 60° C., air was passed over slowly, and the 2-isocyanatoethyl (meth)acrylate was added dropwise while stirring within about half an hour. Stirring was continued until it was no longer possible to observe any NCO band (2261 cm-1) in the IR spectrum. Table 1 shows details of the reaction conditions and the characterization of the inventive writing monomers:

Reference： [1]Current Patent Assignee: COVESTRO AG - US2017/45816, 2017, A1 Location in patent: Paragraph 0252

74
[ 2461-42-9 ]
[ 79-10-7 ]
2-hydroxy-3-(1-naphthyloxy)propyl acrylate [ No CAS ]
1-hydroxy-3-(1-naphthyloxy)propan-2-yl acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,6-di-tert-butyl-4-methyl-phenol; triphenylphosphine at 90℃; for 22.7h;	2.9 General Method for Preparation of the (Meth)Acrylic Acid-Oxirane Adducts (Examples 2.1- 2.11) General procedure: General Method for Preparation of the (Meth)Acrylic Acid-Oxirane Adducts (Examples 2.1- 2.11) (0178) The oxirane, the catalyst, stabilizer and the (meth)acrylic acid were initially charged in a three-neck flask equipped with precision glass stirrer and stirrer motor, and also a drying tube. The mixture was heated to 90° C., and stirring was continued at this temperature until, in the 1H NMR spectrum, a conversion of the oxirane group of >95% was apparent or no oxirane groups were detectable any longer. (MC=main components, SC=secondary component)

Reference： [1]Current Patent Assignee: COVESTRO AG - US2017/45816, 2017, A1 Location in patent: Paragraph 0178; 0231; 0232; 0233; 0234; 0235; 0236; 0237

75
[ 2461-42-9 ]
[ 79-46-9 ]
[ 525-66-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium tetrahydroborate; nickel(II) chloride hexahydrate In water at 20℃; for 24h; Inert atmosphere; Green chemistry;

Reference： [1]Prathap, Kaniraj Jeya; Wu, Qiong; Olsson, Richard T.; Dinér, Peter [Organic Letters, 2017, vol. 19, # 18, p. 4746 - 4749]

76
[ 2461-42-9 ]
1-(2,3-dichloropropoxy)naphthalene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With tetra-(n-butyl)ammonium iodide; 1,2-dichloro-ethane; triphenylphosphine at 80℃; for 4h; Sealed tube; Inert atmosphere;	3.1 Procedure for the preparation of 2 General procedure: Epoxide 1a (1.0 equiv, 0.5 mmol, 60.1 mg), Ph3P (1.2 equiv, 0.6 mmol, 157.4mg), nBu4NI (1.4 equiv, 0.7 mmol, 258.6 mg) and ClCH2CH2Cl (5.0 mL) were added into a 10 mL sealed tube under a N2 atmosphere. The resulting mixture was stirred at 80 °C for 4 h. After the reaction solvent was removed by concentration under vacuum, the residue was subjected to flash column chromatography with hexane/ethyl acetate (100:1-4:1) as the eluent to afford the product 2a.

Reference： [1]Long, Jin; Chen, Jia; Li, Rong; Liu, Zhuo; Xiao, Xuan; Lin, Jin-Hong; Zheng, Xing; Xiao, Ji-Chang [Synlett, 2019, vol. 30, # 2, p. 181 - 184]

77
[ 2461-42-9 ]
4-(2,4-bis(methoxymethoxy)phenyl)piperazine [ No CAS ]
C₂₇H₃₄N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 20 - 70℃; for 10h;	Synthesis of 1-(4-(2,4-dihydroxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy)propan-2-ol (9) To a solution of 2-((naphthalen-1-yloxy)methyl)oxirane (5) (105 mg, 0.52 mmol) in ethanol (1 mL), 4-(2,4-bis(methoxymethoxy)phenyl)piperazine (148 mg, 0.52 mmol) was added at room temperature. After being stirred for 10 h at 70 C, the mixture was cooled and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (chloroform / methanol = 50 / 1) to give compound 7c as a crude product, which was used without further purification. To a solution of compound 7c in dioxane (1 mL), 4N HCl dioxane solution (1 mL) was added at room temperature. After being stirred for 12 h, the reaction mixture was added with a saturated aqueous solution of NaHCO3. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried over anhydrous MgSO4 and were concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (chloroform / methanol = 50 / 1) to give compound 9 (8.0 mg, 10%, 2 steps).

Reference： [1]Fukuhara, Hiroshi; Gotoh, Akinobu; Kino, Yukari; Kurioka, Rina; Mabuchi, Miyuki; Matsunaga, Wataru; Nakao, Syuhei; Shimizu, Tadashi; Tanaka, Akito; Yamaguchi, Keiko; Yamamoto, Momoka [Bioorganic and medicinal chemistry letters, 2020, vol. 30, # 1]

78
[ 2461-42-9 ]
[ 129338-90-5 ]
1-((4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	In ethanol at 20 - 70℃; for 1.5h;	Synthesis of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl) -3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190). To a solution of 3-methoxy-4-(piperazin-1-yl) phenol (9.0 g, 43.4 mmol) in ethanol (60 mL) was added to a solution of ((naphthalen-1-yloxy) methyl)oxirane 5 (8.7 g, 43.4 mmol) in ethanol (30 mL) at room temperature. After being stirred for 1.5 h at 70 C, the mixture was cooled and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (chloroform / methanol = 50 / 1) to give compound 2 (12.7 g, 71%) as a pink solid. MP 115-116 °C. IR (KBr, cm-1) 3031, 2999, 2961, 2911, 2856, 2782, 1509, 1208, 1183, 1149, 1106. 1H-NMR (400 MHz, CDCl3): δ 2.70-2.79 (m, 4H), 2.91-2.94 (dd, J = 10.5 and 5.0 Hz, 2H), 3.04 (br s, 4H), 3.79 (s, 3H), 4.16 (dd, J = 9.6 and 5.0 Hz), 4.23 (dd, J = 9.6 and 5.0 Hz, 1H), 4.28-4.34 (m, 1H), 6.35 (dd, J = 8.2 and 2.7 Hz), 6.41 (d, J = 2.7 Hz, 1H), 6.80 (d, J = 8.2 Hz), 6.83 (d, J = 7.8 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.44 (d, J = 8.6 Hz, 1H) 7.46-7.52 (m, 2H), 7.78-7.82 (m, 1H), 8.24-8.28 (m, 1H); 13C-NMR (100 MHz, CDCl3): δ 51.24 (2C), 53.52 (2C), 55.39, 60.77, 65.53, 70.39, 99.94, 104.78, 106.24, 118.80, 120.55, 121.89, 125.23, 125.50, 125.78, 126.42, 127.45, 134.41, 134.47, 152.20, 153.37, 154.32; ESI-HRMS (positive ion, sodium formate): calcd for C24H29N2O4+ ([M+H]+) 409.2121; found 409.2142.

Reference： [1]Fukuhara, Hiroshi; Gotoh, Akinobu; Kino, Yukari; Kurioka, Rina; Mabuchi, Miyuki; Matsunaga, Wataru; Nakao, Syuhei; Shimizu, Tadashi; Tanaka, Akito; Yamaguchi, Keiko; Yamamoto, Momoka [Bioorganic and medicinal chemistry letters, 2020, vol. 30, # 1]

79
[ 64-18-6 ]
[ 2461-42-9 ]
1-iodo-3-(naphthalen-1-yloxy)propan-2-yl formate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With iodine; triphenylphosphine In toluene at 80℃; Sealed tube;	Typical procedure for the preparation of 1a-13a General procedure: To a solution of triphenylphosphine (1.05 mmol) in anhydrous toluene (2 mL) were added iodine (1.05 mmol) at room temperature, the mixture was stirred for 10 minutes until it became yellow turbid solution. Then epoxide (1 mmol) was added, followed by the addition of formic acid (1.05 mmol). Then the reaction was refluxed for 15 - 40 minutes. After completion of the reaction, the liquid was poured into DCM (20 mL), washed with 5% Na2S2O3 solution (215 mL), water (215 mL) and brine (20 mL).The combined organic layers were dried with anhydrous Na2SO4, filtered and concentrated. The residue was purified by chromatograph on silica gel (petroleum ether/acetone = 50/1, v/v) to give 1a-13a.

Reference： [1]Zhu, Ye-Fu; Wei, Bo-Le; Wang, Wen-Qiong; Xuan, Li-Jiang [Tetrahedron Letters, 2019, vol. 60, # 50]

80
[ 2461-42-9 ]
[ 811-68-7 ]
(3-(naphthalen-1-yloxy)prop-1-en-1-yl)(trifluoromethyl)sulfane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With tetra-(n-butyl)ammonium iodide; potassium iodide In toluene at 80℃; for 6h; Inert atmosphere;	4. General procedure for trifluoromethylthiolation of epoxides General procedure: To a mixture of epoxide 1 or 3 (0.5 mmol, 1.0 equiv) and AgSCF3 (313.4 mg, 1.5 mmol, 3.0 equiv) in toluene (5.0 mL) was added n-Bu4NI (1.67 g, 4.5 mmol, 9.0 equiv) and KI (0.50 g, 3.0 mmol, 6.0 equiv). The reaction mixture was stirred at 80 °C /120 °C under nitrogen atmosphere for 6 h. After the reaction was complete, the reaction mixture was cooled to room temperature and filtered through a plug of silica (eluted with EtOAc). The filtrate was concentrated, and the product was purified by column chromatography on silica gel to give product 2 or 4.

Reference： [1]Chen, Hui-Ting; Huang, Yangen; Qing, Feng-Ling; Xu, Xiu-Hua [Tetrahedron Letters, 2020, vol. 61, # 12]

81
[ 2461-42-9 ]
[ 104-12-1 ]
C₂₀H₁₆ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With C₂₂H₂₄F₆N₃O⁽¹⁺⁾*Br^(1-) In chlorobenzene at 100℃; for 12h; Inert atmosphere;

Reference： [1]Cui, Dong-Xiao; Huang, Ping; Jia, Yan-Yan; Li, Yue-Dan; Tian, Zhuang; Wang, Ping-An [RSC Advances, 2020, vol. 10, # 21]

82
[ 2461-42-9 ]
[ 622-58-2 ]
C₂₁H₁₉NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With C₂₂H₂₄F₆N₃O⁽¹⁺⁾*Br^(1-) In chlorobenzene at 100℃; for 12h; Inert atmosphere;

Reference： [1]Cui, Dong-Xiao; Huang, Ping; Jia, Yan-Yan; Li, Yue-Dan; Tian, Zhuang; Wang, Ping-An [RSC Advances, 2020, vol. 10, # 21]

83
[ 2461-42-9 ]
[ 2493-02-9 ]
C₂₀H₁₆BrNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With C₂₂H₂₄F₆N₃O⁽¹⁺⁾*Br^(1-) In chlorobenzene at 100℃; for 12h; Inert atmosphere;

Reference： [1]Cui, Dong-Xiao; Huang, Ping; Jia, Yan-Yan; Li, Yue-Dan; Tian, Zhuang; Wang, Ping-An [RSC Advances, 2020, vol. 10, # 21]

84
[ 2461-42-9 ]
[ 321-51-7 ]
C₂₆H₂₁FN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere; regioselective reaction;	First step: General procedure: A mixture of 5 (106 mg, 0.5 mmol), epoxide 3 (0.5 mmol) and K2CO3 (103 mg, 0.75 mmol) in DMF (5 mL) was heated at 80 °C under N2 atmosphere for 12 h. The reaction was terminated by the addition of water (10 mL), and then diethyl ether (20 mL) was added. The organic layer was separated, washed by brine (20 mL) and dried over anh. Na2SO4. After filtration, the solution was evaporated to dryness under reduced pressure. The resulting crude product was further dried by a high vacuum pump, and then used it for the next step without further purification.

Reference： [1]Devi, Runjun; Mukhopadhyay, Subhamoy; Jyoti Das, Arup; Kumar Das, Sajal [Tetrahedron Letters, 2020, vol. 61, # 46]

85
[ 2461-42-9 ]
[ 15687-27-1 ]
2-hydroxy-3-(naphthalen-1-yloxy)propyl 2-(4-isobutylphenyl) propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With butyl methyl imidazolium silica sulfate In acetonitrile for 20h; Reflux;	4.3. General procedure for synthesis of new 1,2-diol monoester of IBPderivatives (1a-1o) General procedure: In a round-bottomed flask, it was added IBP (10 mmol), epoxide (12mmol) and 0.2 g [BMIm]SS in 30 mL anhydrous acetonitrile. The reactionmixture was placed on magnetic stirrer under reflux conditionsfor 12-36 h (Fig. 10). After completion of the reaction (TLC check), thecatalyst was separated by a sintered glass, and the solvent was evaporatedin vacuo (rotary evaporator). Then, the residue was diluted inCHCl3 (150 mL) and washed with H2O (3 × 150 mL). Afterward, theproduct was purified by a short column chromatography eluted by solventsdescribed below.

Reference： [1]Soltani Rad, Mohammad Navid; Behrouz, Somayeh; Atashbasteh, Esmaeil; Hashemi, Seyedeh-Sara [Bioorganic Chemistry, 2021, vol. 107]

86
[ 2461-42-9 ]
[ 67-63-0 ]
1-isopropyloxy-3-(naphthalen-1-yloxy)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: isopropyl alcohol With sodium hydride In paraffin oil at 20℃; for 0.25h; Stage #2: 3-(1-naphthyloxy)-1,2-epoxypropane In isopropyl alcohol; paraffin oil at 20℃; for 12h; Stage #3: With hydrogenchloride In water; isopropyl alcohol; paraffin oil

Reference： [1]Faudone, Giuseppe; Bischoff-Kont, Iris; Rachor, Lea; Willems, Sabine; Zhubi, Rezart; Kaiser, Astrid; Chaikuad, Apirat; Knapp, Stefan; Fürst, Robert; Heering, Jan; Merk, Daniel [Journal of Medicinal Chemistry, 2021, vol. 64, # 12, p. 8727 - 8738]

87
[ 2461-42-9 ]
[ 35386-24-4 ]
(2RS)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(naphthalene-1-yloxy)propan-2-ol monohydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	In toluene	2-5 Example 2 2-[(1-naphthyloxy) methyl] oxylan [3]A toluene solution of 1- (2-methoxyphenyl) piperazin [4] was added dropwise to 5.0 g of a toluene solution.After completion of the reaction, the mixture was washed with water and cooled by adding hydrochloric acid. After the suspension is filtered off, it is dried and (2RS) -1- [4- (2-methoxyphenyl) piperazin-1-yl] -3- (naphthalene-1-yloxy) propan-2-ol-1. Hydrochloride dihydrate [5] was obtained (yield 95%)

Reference： [1]Current Patent Assignee: ASTENA HOLDINGS CO LTD - JP2021/104982, 2021, A Location in patent: Paragraph 0026-0029

88
[ 693-98-1 ]
[ 2461-42-9 ]
1-(2-methylimidazol-1-yl)-3-naphthalen-1-yloxypropan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	at 60℃; for 2.5h;	After dissolving Curezol 2MZ-H (Shikoku Chemical Industry Corporation, 1.29g, 15.7mmol) dissolved in 2-propanone (3.5mL) and heated to 60 °C, a small amount of 3-(1-naphthaleneoxy)-1,2-epoxy propane (Dalian Research and Design Institute of Chemical Industry, 3.00g , 15mmol) was gradually added, Then stir at the same temperature for 2.5 hours. The reaction solution was cooled to room temperature, filtered to obtain the precipitated solids, washed with 2-acetone, dried at 50 °C under reduced pressure, and the object of interest was given 2.03g (yield 47%). The measured physical properties of the product are as follows.

Reference： [1]Current Patent Assignee: NAMICS CORPORATION - TW2021/44322, 2021, A Location in patent: Paragraph 0090-0091

CAS No. :	2461-42-9	MDL No. :	MFCD00055643
Formula :	C₁₃H₁₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QYYCPWLLBSSFBW-UHFFFAOYSA-N
M.W :	200.23	Pubchem ID :	91521
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P201-P202-P261-P264-P270-P271-P272-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P308+P313-P330-P333+P313-P337+P313-P363-P403+P233-P405-P501	UN#:	N/A
Hazard Statements:	H302-H319-H335-H341-H351-H317	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 2461-42-9 ] {[proInfo.proName]}

Quality Control of [ 2461-42-9 ]

Related Doc. of [ 2461-42-9 ]

Product Details of [ 2461-42-9 ]

Safety of [ 2461-42-9 ]

Application In Synthesis of [ 2461-42-9 ]

[ 2461-42-9 ] Synthesis Path-Upstream 1~2

[ 2461-42-9 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 2461-42-9 ]

Aryls

Ethers

Related Parent Nucleus of
[ 2461-42-9 ]

Epoxides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 2461-42-9 ] {[proInfo.proName]}

Quality Control of [ 2461-42-9 ]

Related Doc. of [ 2461-42-9 ]

Product Details of [ 2461-42-9 ]

Safety of [ 2461-42-9 ]

Application In Synthesis of [ 2461-42-9 ]

[ 2461-42-9 ] Synthesis Path-Upstream 1~2

[ 2461-42-9 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 2461-42-9 ]

Aryls

Ethers

Related Parent Nucleus of [ 2461-42-9 ]

Epoxides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 2461-42-9 ]

Related Parent Nucleus of
[ 2461-42-9 ]