Name: 54149-17-6|1-Bromo-2-(2-methoxyethoxy)ethane|90% (stabilizedwith Na2CO3)
Brand: Ambeed
SKU: A551995
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1
[ 111-77-3 ]
[ 54149-17-6 ]

Yield	Reaction Conditions	Operation in experiment
	With carbon tetrabromide; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 16h;	Step 1. Synthesis of 1-bromo-2-(2-methoxyethoxy)ethane To a solution of diethylene glycol monomethyl ether (0.698 g, 5.81 mmol) in THF (10 mL) was added triphenylphosphine (1.53 g, 5.83 mol) and carbon tetrabromide (1.93 g, 5.81 mol) at 0 C. After the solution was stirred at room temperature for 16 h, it was quenched with saturated NaHCO3(aq) and extracted with CH2Cl2. The combined organic layers were dried over MgSO4(s), filtered, and concentrated. The residue was purified by flash chromatography (20% ethyl acetate in n-hexane) to give 1-bromo-2-(2-methoxyethoxy)ethane as a yellow liquid. 1H NMR (CDCl3, 300 MHz) delta 3.81 (t, 2H), 3.68-3.65 (m, 2H), 3.57-3.54 (m, 2H), 3.48 (t, 2H), 3.39 (s, 3H).

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2003,vol. 59,p. 1631 - 1641
[2]Synthesis,2003,p. 509 - 512
[3]Collection of Czechoslovak Chemical Communications,1976,vol. 41,p. 1248 - 1252
[4]Journal of Medicinal Chemistry,1995,vol. 38,p. 1067 - 1083
[5]Tetrahedron Letters,2007,vol. 48,p. 4813 - 4815
[6]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1381 - 1384
[7]Patent: US2017/253569,2017,A1 .Location in patent: Paragraph 1254-1255
[8]RSC Advances,2018,vol. 8,p. 36025 - 36033

2
[ 73406-50-5 ]
[ 54149-17-6 ]
3-[2-(2-Methoxy-ethoxy)-ethoxy]-pyridine-2-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 941 - 952

3
[ 54149-17-6 ]
[ 215181-61-6 ]

Yield	Reaction Conditions	Operation in experiment
87.3%	With sodium azide; In water; for 16h;Heating / reflux;	Syntheses of Monofunctional Azides:1-Azido-2-(2-methoxyethoxy)ethane, 19. A solution of 1-bromo-2-(2-methoxyethoxy) ethane (12.4 g, 67.8 mmol) and sodium azide (13.2 g, 203 mmol) in water (150 ml) was stirred under reflux for 16 hours. The aqueous phase was extracted with dichloromethane (2×200 ml), dried with MgSO4 and evaporated to dryness, to give 19 as a colorless oil in 87.3% yield. 1H NMR (500 MHz, CDCl3): delta=3.29 (s, CH3O, 3H), 3.30 (t, J=5.2 Hz, CH2N3, 2H), 3.44-3.48 (m, CH3OCH2, 2H), 3.53-3.60 (m, CH2OCH2, 4H). 13C NMR (125 MHz, CDCl3): delta=50.89 (s, CH2N3, 1C), 59.27 (s, CH3O, 1C), 70.29 (s, CH3OCH2CH2, 1C), 70.84 (s, CH3OCH2CH2, 1C), 72.21 (s, CH2CH2N3, 1C).
	With sodium azide; In N,N-dimethyl-formamide; at 20℃; for 16h;	To a solution of alkyl bromide in dry DMF would be added sodium azide, and the reaction mixture would be stirred at room temperature for 16 h. After completion of the reaction, the contents would be diluted with ethyl acetate and washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo.; 1-Azido-2-(2-methoxy-ethoxy)-ethane (607 mg) was prepared by following General Procedure U starting from 1-bromo-2-(2-methoxy-ethoxy)-ethane (1.0 g) and sodium azide (1.07 g). The crude product was used in the next step without further purification.

Reference： [1]Angewandte Chemie - International Edition,2004,vol. 43,p. 3928 - 3932
[2]Macromolecules,2005,vol. 38,p. 3663 - 3678
[3]Patent: US2009/69561,2009,A1 .Location in patent: Page/Page column 6
[4]Journal of Medicinal Chemistry,1995,vol. 38,p. 1067 - 1083
[5]Patent: US2011/201604,2011,A1 .Location in patent: Page/Page column 117; 149
[6]Angewandte Chemie - International Edition,2012,vol. 51,p. 6971 - 6975

4
[ 54149-17-6 ]
[ 2563-26-0 ]
[ 178813-94-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium hydroxide In ethanol Heating;

Reference： [1]Foley, Sarah; Jones, Gurnos; Liuzzi, Raffaelle; McGarvey, David J.; Perry, Martin H.; Truscott, T. George [Journal of the Chemical Society. Perkin Transactions 2 (2001), 1997, # 9, p. 1725 - 1730]

5
[ 106-41-2 ]
[ 54149-17-6 ]
[ 112968-89-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;	Example 36 Synthesis of N-{4-[2-(2-methoxyethoxy)ethoxy]phenyl}-17-methylmorphinan-3-amine (36), hydrochloride salt Step 1 : Potassium carbonate (839 mg, 6.07 mmol) was suspended in DMF (5 mL). 4-Bromophenol (350 mg, 2.023 mmol) and l-bromo-2-(2-methoxyethoxy)ethane (407 mg, 2.225 mmol) were added to the suspension. The mixture was stirred at 60 C overnight. The reaction mixture was poured into 20 mL of 5% LiCl solution and extracted with ethyl acetate (3 x 30 mL). The organic layer was washed with brine, was dried over sodium sulfate, was filtered and was concentrated. After drying under high vacuum, l-bromo-4-(2-(2- methoxyethoxy)ethoxy)benzene was obtained as colorless oil (537.9 mg) in 97% yield. H NMR (500 MHz, Chloroform-^/) delta 7.36 - 7.31 (m, 2H), 6.80 - 6.74 (m, 2H), 4.10 - 4.07 (m, 2H), 3.84 - 3.82 (m, 2H), 3.70 - 3.68 (m, 2H), 3.56 - 3.55 (m, 2H), 3.37 (s, 3H).
		[0917] To a cooled (0 C.) suspension ofdry NaH (0.512 g,21.4 mmol) in anhydrous DMF (10 mL) under an Argonatmosphere, a solutionof4-bromophenol (3.11 g, 17.8mmol)in anhydrous DMF (20 mL) was added dropwise over 2-3min. The mixture was stirred at oo C. for 10 min and thenallowed to warm to rt over 30 min. To the resulting whitesuspension was added <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong>(2.66 mL, 19.6 mmol) dropwise over 2 min and the mixturewas stirred at rt for 30 min and then at 65 C. for 1.5 h. Aftercooling to rt, the mixture was concentrated under reducedpressure to an oily suspension, diluted with brine (80 mL),and the mixture was extracted with EtOAc (3x60 mL). Thecombined extracts were washed with brine (2x25 mL), driedover Na2 S0 4 , filtered, and concentrated to give compound85a as a mobile, pale amber-colored oil, used inthe following reaction without further purification. Mass spectrum (LCMS,ESI pos.): Calcd. for C 11 H 15Br03 , 275.0/277.0 (M+H).found 275.2/277.1

Reference： [1]Patent: WO2016/182840,2016,A1 .Location in patent: Paragraph 00310
[2]Journal of Materials Chemistry C,2015,vol. 3,p. 9412 - 9424
[3]Bulletin of the Chemical Society of Japan,1997,vol. 70,p. 2519 - 2523
[4]Patent: US2014/364414,2014,A1 .Location in patent: Paragraph 0915-0917

6
[ 929-37-3 ]
[ 54149-17-6 ]
tetraethylene glycol methyl vinyl ether [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-[2-(ethenyloxy)ethoxy]ethan-1-ol With potassium hydride In tetrahydrofuran for 7h; Stage #2: 2-bromoethyl 2-methoxyethyl ether In tetrahydrofuran for 2h;

Reference： [1]Grobelny, Zbigniew; Stolarzewicz, Andrzej; Czaja, Monika; Demuth, Wolfgang; Maercker, Adalbert [Journal of Organic Chemistry, 1999, vol. 64, # 25, p. 8990 - 8994]

7
[ 17334-08-6 ]
[ 54149-17-6 ]
2-[2-(2-methoxy-ethoxy)-ethoxymethyl]-1-methyl-1H-imidazole [ No CAS ]

Reference： [1]Chemical Communications,2005,p. 3832 - 3834

8
[ 54149-17-6 ]
[ 81866-68-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With hydrazine; In ethanol; water; at 0 - 40℃; for 17.3h;	Step 1: [2-(2-Methoxyethoxy)-ethyl]-hydrazine To a solution of hydrazine monohydrate (44.0 mL, 1.00 mol) in ethanol (75 mL) at 0 C. in an ice-water bath was added 1-(2-bromoethoxy)-2-methoxyethane (13.6 mL, 0.100 mol) drop-wise over 20 minutes. The reaction was then allowed to warm to room temperature and stir for 5 minutes and then heated to 40 C. in a preheated oil bath for 12 hours. The reaction was then cooled to room temperature and concentrated to remove the ethanol. The remaining aqueous layer was extracted with methylene chloride (2100 mL) and diethyl ether (2100 mL). The organic layers were combined and dried over anhydrous Na2SO4, filtered and concentrated to provide [2-(2-methoxyethoxy)-ethyl]-hydrazine as a light yellow oil (10.29 g, 85%).
	With hydrazine hydrate;Heating; Inert atmosphere;	Hydrazinemonohydrate and ethanol were put into a reaction container under a nitrogen atmosphere. A compound represented by Formula 1-122-1) was added, rollowed by heating and stirring The resultant product was concentrated to obtain a mixture containing a compound represented ny Formula (i-±2/--L)

Reference： [1]Patent: US2007/225280,2007,A1 .Location in patent: Page/Page column 57
[2]Patent: WO2017/79867,2017,A1 .Location in patent: Page/Page column 171

9
[ 959845-85-3 ]
[ 54149-17-6 ]
1-{1-[2-(2-ethoxyethoxy)ethyl]piperidin-4-yl}-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65.08%		Example 8. 1-{1-[2-(2-ethoxyethoxy)ethyl]piperidin-4-yl}-1W-indazole; To a solution of 1-piperidin-4-yl-1H-indazole TFA salt (0.33 mmol) in DMF (10 ml) was added K2CO3 (137 mg, 0.99 mmol) followed by 1 -bromo-2-(2- ethoxyethoxy)ethane (72 mg, 0.363 mmol). The mixture was heated under N2 atmosphere at 75 "C for 5 hours, cooled down at room temperature and the solvent was evaporated in vacuo. The residue was dissolved in EtOAc (20 ml) and washed <n="29"/>with saturated NaHCO3 (10 ml), brine (10 ml) and dried over sodium sulfate to give the crude compound, which was purified by prep LC/MS - high pH (40-70 % acetonitrile/water to give desired compound as free base. The pure compound was dissolved in CH2CI2 (5 ml) under N2 atmosphere and 1 M solution of hydrochloride in Et2O was added (5 eq.). The mixture was stirred at room temperature for 5 minutes and the solvent was evaporated in vacuo to give the desired compound as HCI salt (76 mg, 65.08 %). MS (M+1 ): 318.3; 1 H NMR (400 MHz, METHANOL-D4): delta ppm 1.21 (t, J = 7.03Hz, 3H), 2.28 (d, J = 13.09Hz, 2H), 2.57 (q, J = 13.67Hz, 2H), 3.36 (br t, J = 12.89Hz, 2H), 3.44 (br t, J = 4.69Hz, 2H), 3.57 (q, J = 7.03Hz, 2H), 3.61 - 3.67 (m, 2H), 3.68 - 3.73 (m, 2H), 3.83 (br s, 1 H), 3.85 - 3.90 (m, 7H), 5.00 (tt, J = 11.40, 7.74, 3.91, 3.71 Hz, 1H), 7.14 - 7.21 (m, 1 H), 7.43 (t, J = 7.32Hz, 1H), 7.67 (d, J = 8.59Hz, 1H), 7.75 (d, J = 7.81 Hz, 1H), 8.05 (s, 1 H).

Reference： [1]Patent: WO2007/142584,2007,A1 .Location in patent: Page/Page column 27

10
[ 54149-17-6 ]
[ 958249-89-3 ]

Yield	Reaction Conditions	Operation in experiment
36%		The tetra-TTF calix[4]pyrroles 2a-i (porphyrinogen derivatives of the present invention) were synthesized as shown in Schemes 3-1 1. Treating the monopyrroIo-TTF derivatives 1a- i with an excess of TFA and in the presence or absence of tetrabutylamonium fluoride (TBAF), tetrabutySarnonium chloride (TBACI), or tetrabutylamonium bromide (TBABr) in a mixture of CH2CI2 and Me2CO gave the tetra-TTF ca I ix[4] pyrroles 2a-i as yellow compounds in 13-55% yields. The tetra-TTF calix[4]pyrroles 2a-i were fully characterized by traditional techniques. The required monopyrrolo-TTF derivatives 1a-b were prepared according to the literature procedures (Hansen et a/ J Mater. Chem, 2004, 14, 179-184 and Jeppesen ef a/. J Org Chem. 2000, 65, 5794-5805), whereas the monopyrroio-TTF derivatives 1c- i were prepared as illustrated in Schemes 12-18.

Reference： [1]Patent: WO2007/132430,2007,A2 .Location in patent: Page/Page column 10; 15; Sheet 15/16

11
[ 552845-71-3 ]
[ 54149-17-6 ]
[ 552845-72-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 3h;	To a solution of 2-hydroxy-4-methoxy-5-thiophen-2-yl-benzaldehyde from EX-LB (0.10 g, 0.43 mmol) in N, N-DIMETHYLFORMAMIDE (3 mL) was added potassium carbonate (0.18 g, 1.3 mmol) and the resulting yellow slurry was heated to 80C. Once at 80 C, 1-BROMO-2-(2-METHOXYETHOXY) ethane (0.24 g, 1.3 mmol) was added dropwise in three equal portions with stirring at 1 h intervals. After the last addition, the reaction was stirred for an additional 1 h at 80 C and cooled to room temperature. The mixture was diluted with water (15 mL) and extracted with ethyl acetate (3 x 15 mL). The combined organic layers was sequentially washed with a saturated ammonium chloride solution (1 X 15 mL), water (1 X 15 mL), and brine (1 X 15 mL), dried over sodium sulfate, and concentrated to a brown oil. Silica gel chromatography (ethyl acetate/hexanes, 4: 1) afforded 0.13 g (87%) of 4-METHOXY-2- [2- (2- methoxyethoxy) ethoxy] -5-thiophen-2-yl-benzaldehyde as a pale yellow OIL.'H-NMR (300 MHz, CDC13) 8 10.38 (s, 1 H), 8.12 (s, 1 H), 7.44 (dd, 1 H), 7.30 (dd, 1 H), 7.07 (dd, 1 H), 6.57 (s, 1 H), 4.33 (t, 2 H), 4.00 (s, 3 H), 3.94 (t, 2 H), 3.74m, 2 H), 3.59 (m, 2 H), 3.40 (s, 3 H). HRMS (EI) Calcd. for CL7H2005S : 336.1031. Found: 336.1027

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1304 - 1315
[2]Patent: WO2004/56727,2004,A2 .Location in patent: Page 59

12
[ 54149-17-6 ]
[ 41489-76-3 ]
[ 956396-68-2 ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 7327 - 7331

13
[ 54149-17-6 ]
[ 31576-51-9 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 1067 - 1083

14
[ 13275-42-8 ]
[ 54149-17-6 ]
[ 815581-76-1 ]

Reference： [1]Patent: WO2004/113351,2004,A2 .Location in patent: Page 22; 30

15
[ 249292-10-2 ]
[ 54149-17-6 ]
6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-(2-(2-methoxy-ethoxy)-ethyl)-2H-pyridazin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 150℃; for 1h;Microwave heating;	Example 9. 6-{4-[4-(5-Chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-[2-(2-methoxv-ethoxv)-ethvll-2H-pvridazin-3-one. 6- [4- ( {4- [ (5-Chloro-lH-indol-2-yl) sulphonyl] piperazin-1-yl} carbonyl) phenyl]- pyridazin-3-ol (see WO 99/57113,0. 054 gram, 0.11 mmol), 0. 016 gram of anhydrous potassium carbonate (0.11 mmol, 1.0 eq. ) and 0.02 gram of 1-bromo-2-(2-methoxy- ethoxy) ethane (0.11 mmol, 1.0 eq. ) were mixed in 1.5 mL of dry N, N-dimethylformamide. The mixture was treated with microwave at 150 C for 1 hour. Without any work-up, purification was performed on preparative HPLC, which gave 0.023 gram of 6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-[2-(2- methoxy-ethoxy)-ethyl]-2H-pyridazin-3-one (yield 36 %).

Reference： [1]Patent: WO2005/65688,2005,A1 .Location in patent: Page/Page column 24

16
[ 54149-17-6 ]
[ 304465-35-8 ]
C₂₃H₂₀N₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 48h;	A mixture of intermediate f (105 mg, 0.318 mmol), 1-bromo-2-(2-methoxyethoxy)- ethane (76 mg, 0.41 mmol), and K2C03 (57 mg, 0.41 mmol) in DMF (5 ml) was stirred at room temperature for 48 hours. The reaction mixture was partitioned between water (20 ml) and ethyl acetate (30 ml), dried (Na2S04) and evaporated. The residue was triturated in diethyl ether (3 ml), and filtered off. The yellow prisms were washed with diethyl ether and hexane to give the target product 4 (51 mg, yield = 37%).

Reference： [1]Patent: WO2005/111034,2005,A1 .Location in patent: Page/Page column 69-70

17
[ 16433-88-8 ]
[ 54149-17-6 ]
[ 180690-29-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; In water; dimethyl sulfoxide; at 20℃; for 2h;	Example 9 Synthesis of 2,7-Dibromo-9,9-bis(3,6-dioxaheptyl)-fluorene Benzyltriethylammonium chloride (3.19 g, 14 mmole, 0.077 eq) and 2,7-dibromofluorene (59 g, 182 mmole, 1 eq) were suspended in 178 mL DMSO. 50% aqeous NaOH (80 mL) was added. <strong>[54149-17-6]1-Bromo-2-(2-methoxyethoxy)ethane</strong> (80 g, 437 mmole, 2.4 eq) was then added in small portions. The reaction was stirred at room temperature for 2 hours before it was stopped and the aqueous layer was extracted with ether. The combined ether layers were washed with water five times and dried over Na2SO4. The organic layer was filtered, evaporated to dryness, and the residual was flash chromatographed on a silica-gel column to give 73 g of the pure compound in a yield of 86%.
86%	With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; In dimethyl sulfoxide;	Example 20 Synthesis and Utility of 2,7-dibromo-9,9-bis(3,6-dioxaheptyl)-fluorene Benzyltriethylammonium chloride (3.19 g, 14 mmole, 0.077 eq) and 2,7-dibromofluorene (59 g, 182 mmole, 1 equiv.) were suspended in 178 mL DMSO. 50% aqeous NaOH 80 mL was added. <strong>[54149-17-6]1-Bromo-2-(2-methoxyethoxy)ethane</strong> (80 g, 437 mmole, 2.4 equiv.) was then added in small portions. The reaction was stirred at room temperature for 2 hours before it was stopped and the aqueous layer was extracted with ether. The combined ether layers were washed with water five times and dried over Na2SO4. The organic layer was filtered, evaporated to dryness and the residual was flash chromatographed on a silica-gel column to give the pure compound (73 g), in a yield of 86%. This compound can be used for example to modify the solubility parameter of the compound of Example 16. To do this 2,7-dibromo-9,9-bis(3,6-dioxaheptyl)-fluorene is used in place of 2,7-dibromo-9,9-dioctyl fluorene in Example 16.
80%	With iodine; dimethyl sulfoxide; potassium hydroxide; at 20℃; for 24h;	To a dimethylsalenium suspension (130 mL) of 2,7-dibromo (6.48 g, 20 mmol) (manufactured by Tokyo Chemical Industry Co., Ltd.), potassium hydroxide (5.61 g, 100 mmol) (0.33 g, 2 mmol) and 1-bromo-2- (2-methoxyethoxy) ethane (8.05 g, 44 mmol) and stirred at room temperature for 24 hours. After completion of the reaction, the mixture was cooled to 0 C, and water (120 mL) was added thereto, followed by neutralization with hydrochloric acid. The organic layer was extracted with ethyl acetate and dried over magnesium sulfate. The crude product was concentrated and purified by silica gel column chromatography (eluent: eluent / ethyl acetate (4/1 - & gt; 3/1)) to give Compound 1 (yield 8.47 g, yield: yellow liquid)80%).

40%

2,7-dibromofluorene (Sigma Aldrich) (15.7 g, 0.048 mol) was dissolved in anhydrous tetrahydrofuran (150 mL) and cooled to 5 C. under argon atmosphere. Sodium tert-butoxide (10.5 g, 0.109 mol) was added portionwise, giving a deep red colour. After completion of addition, the reaction mixture was stirred at room temperature for 20 minutes. A solution of <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (Sigma Aldrich) (20 g, 0.109 mol) in anhydrous THF (50 mL) was added dropwise. The solution turned dark purple and an exotherm to 30 C. was observed. The reaction mixture was stirred at room temperature for 72 hours then diluted with water and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate (2*). The combined organic layers were washed with water and brine then dried (Na2SO4) and filtered. Concentration of the filtrates in vacuo followed by purification of the residue by dry flash chromatography (0 to 40% ethyl acetate in heptane) gave 2,7-dibromo-9,9-Bis[2-(2-methoxyethoxy)ethyl]-9H-fluorene as a yellow oil (10 g, 40%). 1H NMR (300 MHz, CDCl3) 7.52-7.42 (m, 6H), 3.27 (m, 10H), 3.16 (m, 4H), 2.76 (m, 4H), 2.34 (m, 4H).

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 9525 - 9529
[2]Patent: US7094902,2006,B2 .Location in patent: Page/Page column 92
[3]Patent: US7271406,2007,B2
[4]Patent: TW2016/2059,2016,A .Location in patent: Paragraph 0117; 0118
[5]Patent: US2019/131533,2019,A1 .Location in patent: Paragraph 0597-0600

18
[ 186435-66-5 ]
[ 54149-17-6 ]
[ 484682-45-3 ]

Yield	Reaction Conditions	Operation in experiment
42%	With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate; In acetone;	6-Amino-2-methoxy-3-[2-(2-methoxyethoxy)ethyl]-4-pyrimidone The mixture of <strong>[186435-66-5]6-amino-2-methoxy-4-pyrimidone</strong> (1 eq), potassium carbonate (1.5 eq), benzyltriethylammonium chloride (0.3 eq) and 2-(2-methoxyethoxy)ethyl bromide (1.5 eq) in acetone was heated at reflux overnight. After cooling to room temperature, the insoluble salts were filtered off and the solvent was removed. The residue was purified by chromatography on silica gel with chloroform:methanol (98:2-95:5) as eluent, to give 6-amino-2-methoxy-3-[2-(2-methoxyethoxy)ethyl]-4-pyrimidone (yield 42%) as a white solid. 300 MHz 1H NMR (DMSO-d6): delta 3.22 (s, 3H, CH3O), 3.38 (m, 2H, CH2O), 3.47 (m, 4H, 2*CH2), 3.85 (s, 3H, CH3O), 3.91 (t, 2H, CH2N), 4.81 (s, 1H, C5-H), 6.36 (s, 2H, NH2) ppm.

Reference： [1]Patent: US2003/114445,2003,A1

19
[ 17229-14-0 ]
[ 54149-17-6 ]
[ 17403-09-7 ]
[2-(4-{1-[2-(2-methoxy-ethoxy)-ethyl]-1H-indol-3-yl}-piperidin-1-yl)-ethoxy]-acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%		EXAMPLE 36 Preparation of [2-(4-{1-[2-(2-methoxy-ethoxy)-ethyl]-1H-indol-3-yl}-piperidin-1-yl)-ethoxy]-acetic acid The procedure described in Example 1 was performed using 0.2 g (1 mmol) of 3-piperidin-4-yl-1H-indole and 0.18 g (1.1 mmol) of <strong>[17229-14-0](2-chloro-ethoxy)-acetic acid ethyl ester</strong>. 0.06 g (0.18 mmol) of the crude, obtained as in step D, were then alkylated with 0.03 mL (0.27 mmol) of 1-bromo-2-(2-methoxy-ethoxy)-ethane affording 0.056 g (77% yield) of [2-(4-{1-[2-(2-methoxy-ethoxy)-ethyl]-1H-indol-3-yl}-piperidin-1-yl)-ethoxy]-acetic acid. ESI/MS m/e=405 [(M+1)+, C22 H32 N2 O5] NMR (300 MHz, CDCl3) d=2.05-2.40 (m, 4H), 2.89-3.05 (m, 5H), 3.36 (s, 3H), 3.47-3.57 (m, 4H), 3.67-3.81 (m, 4H), 3.87-3.91 (t, 2H), 4.10 (s, 2H), 4.24-4.28 (t, 2H), 7.02-7.27 (m, 3H), 7.35-7.37 (d, 1H), 7.56-7.58 (d, 1H)

Reference： [1]Patent: US2002/147344,2002,A1

20
(+/-)-3-(trans-3,4-dimethylpiperidinyl)phenol [ No CAS ]
[ 54149-17-6 ]
(+/-)-3-{1-[2-(2-methoxyethoxy)ethyl]-trans-3,4-dimethylpiperidinyl}phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydrogencarbonate; In water; N,N-dimethyl-formamide; acetonitrile;	Example 7 (+-)-3-{1-[2-(2-Methoxyethoxy)ethyl]-trans-3,4-dimethylpiperidinyl}phenol To a solution of (+-)-3-(trans-3,4-dimethylpiperidinyl)phenol (60 mg, 0.29 mmol) in N,N-dimethylformamide (5.0 mL) at room temperature was added sodium hydrogencarbonate (27 mg, 0.32 mmol), and <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (59 mg, 0.32 mmol). The solution was heated at 120 C. for 1 hour, cooled and then water (10 mL) was added. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give a crude oil. This was purified by preparative HPLC on a Dynamax column, 42*250 mm; flow 8.0 mL min-1; employing U.V. detection at 275 nm; eluant gradient of acetonitrile:0.05 M aqueous ammonium acetate solution (90:10 to 10:90) to afford the title compound (71 mg, 80%) as its acetate salt. 1H-NMR (data for the acetate salt): 0.82 (d, 3H), 1.35 (s, 3H), 1.72 (m, 1H), 2.03-2.10 (m, 4H), 2.38 (m, 1H), 2.81-3.13 (m, 6H), 3.40 (s, 3H), 3.50-3.63 (m, 4H), 3.70-3.78 (m, 2H), 6.68 (m, 1H), 6.81-6.82 (m, 2H), 7.18 (t, 1H). MS (TSI+): m/z [MH+] 308.3; C18H29NO3+H requires 308.2.

Reference： [1]Patent: US6518282,2003,B1

21
[ 54149-17-6 ]
[ 16881-33-7 ]
[ 179187-74-7 ]

Yield	Reaction Conditions	Operation in experiment
		f N-Benzyloxycarbonyl-3-[4-(1,4,7-trioxaoctyl)-phenyl]-alanine-tert-butyl ester 7.43 g (20 mmol) of N-benzyloxycarbonyl-tyrosine-tert-butyl ester is reacted with 1-bromo-2-(2-methoxyethoxy)-ethane to alkylated phenol analogously to Example a). Yield: 8.2 g (86.6% of theory) of colorless oil.

Reference： [1]Patent: US5885548,1999,A

22
[ 4920-77-8 ]
[ 54149-17-6 ]
1-[2-(2-methoxyethoxy)ethoxy]-3-methyl-2-nitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In water; N,N-dimethyl-formamide;	EXAMPLE 6 A mixture containing <strong>[4920-77-8]3-methyl-2-nitrophenol</strong> (30.6 g; 0.2 mole), 2-(2-methoxy)ethoxybromoethane (40.2 g; 0.22 mole) and potassium carbonate (30.5 g; 0.22 mole) in 300 ml. of dimethyl formamide was refluxed for 24 hours. The reaction mixture was cooled to 26 C. and then 200 ml. of water was added to the reaction mixture. The resulting mixture was extracted into methylene chloride and the organic methylene chloride layer was washed with sodium hydroxide, then water, dried over magnesium sulfate and concentrated in vacuo to yield an oil residue. The residue was distilled at 127 C. (0.07 mmHg) to yield 45.3 g of 1-[2-(2-methoxyethoxy)ethoxy]-3-methyl-2-nitrobenzene as a yellow oil.
	With potassium carbonate; In water; N,N-dimethyl-formamide;	(a) A mixture containing <strong>[4920-77-8]3-methyl-2-nitrophenol</strong> (30.6 g; 0.2 mole), 2-(2-methoxy)ethoxybromoethane (40.2 g; 0.22 mole) and potassium carbonate (30.5 g; 0.22 mole) in 300 ml. of dimethyl formamide was refluxed for 24 hours. The reaction mixture was cooled to 26 C. and then 200 ml. of water was added to the reaction mixture. The resulting mixture was extracted into methylene chloride and the organic methylene chloride layer was washed with sodium hydroxide, then water, dried over magnesium sulfate and concentrated in vacuo to yield an oil residue. The residue was distilled at 127 C. (0.07 mmHg) to yield 45.3 g of 1-[2-(2-methoxyethoxy)ethoxy]-3-methyl-2-nitrobenzene as a yellow oil.

Reference： [1]Patent: US4332614,1982,A
[2]Patent: US4451285,1984,A

23
[ 1660-95-3 ]
[ 54149-17-6 ]
[ 112-02-7 ]
[ 203307-70-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; ammonium chloride; In tetrahydrofuran; water; ethyl acetate;	Example 1 The following is a procedure for the synthesis of 1,1-diphosphono-4,7-dioxaoctane (DPDO). Under an inert nitrogen atmosphere, sodium hydride (2.01 g, 0.088 mole) was combined with 200mL dry tetrahydrofuran (THF) in a three-necked 500 mL roundbottom flask equipped with a nitrogen sweep and magnetic stirrer. The resulting suspension was cooled to -10C in an ice/salt bath and stirred. A solution of tetraisopropyl methylenediphosphonate (27.5 g, 0.08 mole) dissolved in 30 mL dry THF was then added dropwise over a 90 minute period via an addition funnel. The reaction mixture was then allowed to stir for 30 min at -10C and 1 hour at room temperature. A solution of 1-bromo-2-(2-methoxyethoxy)ethane (16.8 g, 0.092 mole) dissolved in 25 mL dry THF was then added dropwise over a 1 hour period. The reaction solution was then allowed to stir for 2 hours at room temperature and overnight (18 hours) at reflux. The reaction was then quenched with 5 mL 10 wt % ammonium chloride, filtered, concentrated, and dissolved in 500mL ethyl acetate. The ethyl acetate solution was washed in a separatory funnel with saturated sodium chloride, dried with magnesium sulfate, filtered, and concentrated to 33.1 g amber oil product. The product was comprised of a mixture of the tertraisopropyl ester of 1,1-diphosphono-4, 7-dioxaoctane /tetraisopropyl methylenediphosphonate / phosphorus-containing byproducts in a 56/35/9 mole ratio, along with some unreacted bromo-2-(2-methoxyethoxy)ethane. The intermediate alkylation product mixture (32 g) described above was placed in a 2L round bottom flask. A solution of 5% hydrochloric acid (836 g) containing <strong>[112-02-7]cetyltrimethylammonium chloride</strong> (0.020 g) was then added slowly with stirring. The reaction was then heated to reflux and stirred for 24 hours. The reaction solution was then concentrated to 19.4 g oil, then dissolved in water to a total weight of 149 g. The product-was analyzed for total phosphorus content and by phosphorus and carbon NMR, which showed a 9.2 wt % mixture of DPDO/(MDP) methylene diphosphonate/phosphorus-containing byproduct in a 54/38/8 mole ratio.

Reference： [1]Patent: EP950029,2002,B1

24
[ 54149-17-6 ]
[ 84905-80-6 ]
[ 919278-13-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h;	A mixture of 4-chloro-5H-pyrrolo [3, 2-d] pyrimidine (768 EPO <DP n="116"/>nag, 5.0 mmol) , l-bromo-2- (2-methoxyethoxy) ethane (90%, 1000 mg, 4.9 mmol), cesium carbonate (2118 mg, 6.5 mmol) and N, N- dimethylformamide (5 mL) was stirred at room temperature for 18 hr. The reaction mixture was diluted with water and 5 extracted with ethyl acetate (chi3) . The organic layer was concentrated under reduced pressure, and the residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=90/10_>0/100) to give the title compound (1173 mg, 93%) as a pale-yellow oil.10 1H-NMR (CDCl3, 300 MHz) delta 3.31 (3H, s), 3.40 - 3.50 (2H, m) , 3.50 - 3.60 (2H, m) , 3.88 (2H, t, J = 5.1 Hz), 4.74 (2H, t, J = 5.1 Hz), 6.86 (IH, d, J = 3.3 Hz), .7.74 (IH, d, J = 3.3 Hz), 8.76 (IH, s) .

Reference： [1]Patent: WO2007/4749,2007,A1 .Location in patent: Page/Page column 114-115

25
[ 926295-27-4 ]
[ 54149-17-6 ]
ethyl (2E)-3-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}-4-[2-(2-methoxyethoxy)ethoxy]phenyl}acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 50℃;	To a solution of .ethyl (2E) -3- (2-{ [3-chloro-5-(trifluoromethyl) pyridin-2-yl] oxy}-4-hydroxyphenyl) acrylate (5.12 g) in N, N-dimethylformamide (30 ml) were added potassium carbonate (3.66 g) , sodium iodide (3.89 g) and l-bromo-2- (2- methoxyethoxy) ethane (3.60 ml), and the mixture was stirred' overnight at 500C. Then, potassium- carbonate (7.21 g) and 1- bromo-2- (2-methoxyethoxy) ethane (7.20 ml) were added, and the mixture was further stirred for 4 hr. After allowing to cool to room temperature, a saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed EPO <DP n="231"/>with water and saturated brine, dried (MgSO4) , filtrated and ' concentrated. The obtained residue was .subjected to silica gel column chromatography, and eluted with ethyl acetate-hexane (1:19 - 3:2, v/v) to give a white solid. Recrystallization from ethyl acetate-hexane gave ethyl (2E) -3-{2-{ [3-chloro-5- (trifluoromethyl)pyridin-2-yl]oxy}-4- [2- (2- methoxyethoxy) ethoxy] phenyl }acrylate (5.57 g, yield: 86%) as white crystals, melting point 76.6-7beta.8C.

Reference： [1]Patent: WO2007/18314,2007,A2 .Location in patent: Page/Page column 229-230

26
[ 491875-13-9 ]
[ 54149-17-6 ]
[ 912999-91-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate;potassium iodide; In N,N-dimethyl-formamide; at 60℃; for 43.5h;	1-(2-Bromo-ethoxy)-2-methoxy-ethane (107 mg, 0.58 mmol) was added to a suspension of 4- hydroxy-2-(4-methoxy-benzyl)-isoindole-1 ,3-dione (150 mg, 0.53 mmol) and potassium carbonate (200 mg, 1.4 mmol) in DMF (2 mL). After 3.5 hours, a catalytic amount of potassium iodide was added. After a further 17 hours, the mixture was warmed to 60C. After 3 hours, an additional <n="211"/>amount of 1-(2-bromo-ethoxy)-2-methoxy-ethane (20 mg, 0.11 mmol) was added and the mixture maintained at 600C for a further 20 hours. The mixture was concentrated in vacuo then the residue was taken up in ethyl acetate and washed with potassium carbonate solution and brine. The organic phase was dried (MgSO4) and concentrated to give the title compound as a yellow oil (149 mg, 73%). 1H NMR (methanol-d4) 7.71 (1H, t), 7.43-7.40 (2H, m), 7.31-7.27 (2H, m), 6.87-6.83 (2H, m), 4.71 (2H, s), 4.37-4.34 (2H, m), 3.92-3.89 (2H, m), 3.77-3.74 (5H, m), 3.55-3.53 (2H, m), 3.33 (3H, s). MS: [M+H]+ 386.PREPARATION C11 2-(2.4-Dimethoxy
73%	With potassium carbonate;potassium iodide; In N,N-dimethyl-formamide; at 60℃; for 43.5h;	1-(2-Bromo-ethoxy)-2-methoxy-ethane (107 mg, 0.58 mmol) was added to a suspension of 4- hydroxy-2-(4-methoxy-benzyl)-isoindole-1 ,3-dione (150 mg, 0.53 mmol) and potassium carbonate (200 mg, 1.4 mmol) in DMF (2 mL). After 3.5 hours, a catalytic amount of potassium iodide was added. After a further 17 hours, the mixture was warmed to 60C. After 3 hours, an additional amount of 1-(2-bromo-ethoxy)-2-methoxy-ethane (20 mg, 0.11 mmol) was added and the mixture <n="233"/>maintained at 6O0C for a further 20 hours. The mixture was concentrated in vacuo then the residue was taken up in ethyl acetate and washed with potassium carbonate solution and brine. The organic phase was dried (MgSO4) and concentrated to give the title compound as a yellow oil (149 mg, 73%). 1H NMR (methanol-d4) 7.71 (1 H, t), 7.43-7.40 (2H, m), 7.31-7.27 (2H, m), 6.87-6.83 (2H, m), 4.71 (2H, s), 4.37-4.34 (2H, m), 3.92-3.89 (2H, m), 3.77-3.74 (5H, m), 3.55-3.53 (2H, m), 3.33 (3H, s). MS: [M+H]+ 386.
73%		1-(2-Bromo-ethoxy)-2-methoxy-ethane (107 mg, 0.58 mmol) was added to a suspension of 4- hydroxy-2-(4-methoxy-benzyl)-isoindole-1,3-dione (150 mg, 0.53 mmol) and potassium carbonate (200 mg, 1.4 mmol) in DMF (2 mL). After 3.5 hours, a catalytic amount of potassium iodide was added. After a further 17 hours, the mixture was warmed to 600C. After 3 hours, an additional amount of 1-(2-bromo-ethoxy)-2-methoxy-ethane (20 mg, 0.11 mmol) was added and the mixture maintained at 600C for a further 20 hours. The mixture was concentrated in vacuo then the residue was taken up in ethyl acetate and washed with potassium carbonate solution and brine. The organic phase was dried (MgSO4) and concentrated to give the title compound as a yellow oil (149 mg, 73%). 1H NMR (methanol-d4) 7.71 (1 H, t), 7.43-7.40 (2H, m), 7.31-7.27 (2H, m), 6.87-6.83 (2H, m), 4.71 (2H, s), 4.37-4.34 (2H, m), 3.92-3.89 (2H, m), 3.77-3.74 (5H, m), 3.55-3.53 (2H, m), 3.33 (3H, s). MS: [M+H]+ 386.

73%		1-(2-Bromo-ethoxy)-2-methoxy-ethane (107 mg, 0.58 mmol) was added to a suspension of 4- hydroxy-2-(4-methoxy-benzyl)-isoindole-1,3-dione (150 mg, 0.53 mmol) and potassium carbonate (200 mg, 1.4 mmol) in DMF (2 ml_). After 3.5 hours, a catalytic amount of potassium iodide was added. After a further 17 hours, the mixture was warmed to 6O0C. After 3 hours, an additional amount of 1-(2-bromo-ethoxy)-2-methoxy-ethane (20 mg, 0.11 mmol) was added and the mixture maintained at 600C for a further 20 hours. The mixture was concentrated in vacuo then the residue was taken up in ethyl acetate and washed with potassium carbonate solution and brine. The organic phase was dried (MgSO4) and concentrated to give the title compound as a yellow oil (149 mg,73%). 1H NMR (methanol-d4) 7.71 (1 H, t), 7.43-7.40 (2H, m), 7.31-7.27 (2H, m), 6.87-6.83 (2H, m), 4.71 (2H, s), 4.37-4.34 (2H, m), 3.92-3.89 (2H, m), 3.77-3.74 (5H, m), 3.55-3.53 (2H, m), 3.33 (3H, s). MS: [M+H]+ 386.
73%		1-(2-Bromo-ethoxy)-2-methoxy-ethane (107 mg, 0.58 mmol) was added to a suspension of 4-hydroxy-2-(4-methoxy-benzyl)-isoindole-1,3-dione (150 mg, 0.53 mmol) and potassium carbonate (200 mg, 1.4 mmol) in DMF (2 mL). After 3.5 hours, a catalytic amount of potassium iodide was added. After a further 17 hours, the mixture was warmed to 60 C. After 3 hours, an additional amount of 1-(2-bromo-ethoxy)-2-methoxy-ethane (20 mg, 0.11 mmol) was added and the mixture maintained at 60 C. for a further 20 hours. The mixture was concentrated in vacuo then the residue was taken up in ethyl acetate and washed with potassium carbonate solution and brine. The organic phase was dried (MgSO4) and concentrated to give the title compound as a yellow oil (149 mg, 73%). 1H NMR (methanol-d4) 7.71 (1H, t), 7.43-7.40 (2H, m), 7.31-7.27 (2H, m), 6.87-6.83 (2H, m), 4.71 (2H, s), 4.37-4.34 (2H, m), 3.92-3.89 (2H, m), 3.77-3.74 (5H, m), 3.55-3.53 (2H, m), 3.33 (3H, s). MS: [M+H]+ 386.

Reference： [1]Patent: WO2008/44029,2008,A1 .Location in patent: Page/Page column 209-210
[2]Patent: WO2008/44041,2008,A1 .Location in patent: Page/Page column 231-232
[3]Patent: WO2008/44045,2008,A1 .Location in patent: Page/Page column 284
[4]Patent: WO2008/44054,2008,A2 .Location in patent: Page/Page column 128
[5]Patent: US2010/152184,2010,A1 .Location in patent: Page/Page column 76

27
[ 288-32-4 ]
[ 54149-17-6 ]
[ 798571-53-6 ]

Yield	Reaction Conditions	Operation in experiment
70%		Example 1: Synthesis of ironflID /wgyo-tetrakis(N.N-di-(2-(2-methoxyethoxy)ethv?- imidazol-2-vnporphyrin (6) ;("FeTDPImP")FeTDPImp (FW: 1626.2 g/mol) was synthesized from a starting imdizaole compound using the following synthetic scheme. The synthetic scheme is shown, along with structures of intermediate products, in FIGS. 2A and 2B.1. Synthesis of N-( 2-(2-methoxyethoxy)ethvI>imidazole (2)Imidazole Ig (0.015 mol) was dissolved in dry DMF 50 mL under argon atmosphere. After a NaH mineral oil dispersion (60%) 0.68g (0.017mol) was added, the mixture was heated at 80 0C for 70 min. After cooling to room temperature, l-Bromo-2- (2-methoxyethoxy)-ethane (1), 2.75 g (0.015 mol), was added, then stirred overnight. The reaction was poured into water, extracted by CHCb, washed by water, dried over Na?SCU, then dried (Rotavap) until an oily residue remained. The crude product was purified with silica gel flash column chromatography with an eluant of CHCh : CH3<_)H=20: 1. 1.69 g(70% yield) of the product (2) was obtained as a colorless oil. As an alternative to column <n="30"/>chromatography, product (2) is purified by vacuum distillation
0.1 mol		Synthetic procedures of the zwitterionic compounds reported in previously published papers (Kuroda, K.; Satria, H.; Miyamura, K.; Tsuge, Y.; Ninomiya, K.; Takahashi, K. Journal of the American Chemical Society 2017, 139, 16052-16055; Yoshizawa-Fujita, M.; Tamura, T.; Takeoka, Y.; Rikukawa, M. Chemical Communications 2011, 47, 2345-2347) were used for this Example. Briefly, 0.2 mol sodium hydride was suspended in tetrahydrofuran (THF) under argon gas. Imidazole (0.1 mol), which was dissolved in 30 mL THF, was added dropwise to the sodium hydride solution. After stirring for 24 h at room temperature, <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (0.1 mol) was added to the solution. The resulting suspension was filtered after stirring for 6 h at 70 C. to remove the white precipitate. The solvent was removed by rotary evaporation to yield the crude product. The product was further purified by distillation under reduced pressure. A fraction was collected at 105 C. under reduced pressure to obtain 1-(2-(2-methoxyethoxy)ethyl)-1H-imidazole (OE2im). OE2im (0.1 mol) was subsequently dissolved in 40 mL acetonitrile. 1,4-butanesultone (0.1 mol) was added dropwise to the solution under a nitrogen atmosphere. The mixture was then refluxed for 40 h. The solvent was then removed by rotary evaporation. The residue was washed several times with diethyl ether by decantation followed by drying of the product under vacuum at 50 C. for 24 h to obtain IL 1, 3-(1-(2-Methoxyethyl)-1H-imidazol-3-ium-3-yl)butane-1-sulfonate (OE2imC4S) as a colorless viscous liquid. The zwitterionic compounds IL 2, 3-(1-octyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate (C8imC3S), and IL 4, 3-(1-octyl-1H-imidazol-3-ium-3-yl)butane-1-sulfonate (C8imC4S), were prepared in similar procedure using octylimidazole with 1,3-propanesultone or 1,4-butanesultone.

Reference： [1]Patent: WO2008/45358,2008,A1 .Location in patent: Page/Page column 27-28
[2]Chemical Communications,2011,vol. 47,p. 2345 - 2347
[3]Journal of the American Chemical Society,2017,vol. 139,p. 16052 - 16055
[4]Patent: US2019/360979,2019,A1 .Location in patent: Paragraph 0115-0116

28
[ 61346-19-8 ]
[ 54149-17-6 ]
[ 1133430-64-4 ]

Yield	Reaction Conditions	Operation in experiment
61%	With sodium hydroxide; potassium iodide; In 1,4-dioxane; water; at 60℃;	A mixture of 5-nitro-1,2-dihydro-indazol-3-one (399 mg, 2.22 mmol), 1-bromo-2-(2-methoxy-ethoxy)-ethane (454 uL, 3.34 mmol), potassium iodide (370 mg, 2.22 mmol) and 1N sodium hydroxide solution (6.7 mL, 6.7 mmol) in 2 ml dioxane was stirred at 60 C. overnight. The reaction mixture was then cooled, poured into 50 mL H2O and 300 muL 10N NaOH was added. The aqueous layer was extracted with CH2Cl2 and then acidified to pH 2 with 6N HCl. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over MgSO4, filtered and evaporated. The residue was purified by flash chromatography to afford the product 1-[2-(2-methoxy-ethoxy)-ethyl]-5-nitro-1,2-dihydro-indazol-3-one (380 mg, 61%). ES-MS calcd for C12H15N3O5 (m/e) 281.26, obsd 282.17 (M+H).
61%	With sodium hydroxide; potassium iodide; In 1,4-dioxane; water; at 60℃;	Preparation of 1-[2-(2-methoxy-ethoxy)-ethyl]-5-nitro-1,2-dihydro-indazol-3-one A mixture of 5-nitro-1,2-dihydro-indazol-3-one (399 mg, 2.22 mmol), 1-bromo-2-(2-methoxy-ethoxy)-ethane (454 muL, 3.34 mmol), potassium iodide (370 mg, 2.22 mmol) and 1N sodium hydroxide solution (6.7 mL, 6.7 mmol) in 2 ml dioxane was stirred at 60 C. overnight. The reaction mixture was then cooled, poured into 50 mL H2O and 300 L 10N NaOH was added. The aqueous layer was extracted with CH2Cl2 and then acidified to ~pH 2 with 6N aqueous HCl. The aqueous layer was extracted with ethyl acetate. The combined organic layer dried over MgSO4, filtered and evaporated. The residue was purified by flash chromatography to afford the product 1-[2-(2-methoxy-ethoxy)-ethyl]-5-nitro-1,2-dihydro-indazol-3-one (380 mg, 61%). ES-MS calcd for C12H15N3O5 (m/e) 281.26, obsd 282.17 (M+H).

Reference： [1]Patent: US2009/76275,2009,A1 .Location in patent: Page/Page column 10
[2]Patent: US2009/163546,2009,A1 .Location in patent: Page/Page column 5-6

29
[ 1037247-06-5 ]
[ 54149-17-6 ]
[ 1052245-47-2 ]

Yield	Reaction Conditions	Operation in experiment
69.3%		<Example 3> (Synthesis of Charge Transporting Compound L); [Show Image] Under nitrogen atmosphere, Compound G (0.17 g, 0.31 mmol) and 9.5 g of N,N-dimethylformamide were placed in a 50-ml three-necked flask, and 0.03 g (0.63 mmol) of sodium hydride (60% oil dispersion) was added thereto. Then, the mixture was stirred for 30 minutes. The temperature was raised to 50C. Then, 0.07 g (0.41 mmol) of the above-described halogen compound K was added dropwise thereto, and the mixture was stirred for 7 hours. The reaction liquid was poured into 20 ml of water, and extraction was performed twice with 20 ml of ethyl acetate. The obtained organic layer was washed twice with 20 ml of water. After the organic layer was concentrated by using an evaporator, the obtained residue was purified by silica gel chromatography (10 g of silica gel was used; elution was performed by using 200 ml of hexane/ethyl acetate =2:1 (volume ratio) ; and further elution was performed by using 200 ml of ethyl acetate). Thus, 0.14 g (Yield: 69.3%) of Compound L was obtained. 1H-NMR (270 MHz, CDCl3): delta 2.01 (m, 2H), 2.89 (t, 2H), 3,37 (s, 3H), 3.48-3.58 (m, 4H), 3.58-3.70 (m, 6H), 7.20-7.35 (m, 4H), 7.35-7.53 (m, 7H), 7.63 (d, 4H), 7.81 (d, 4H), 7.98 (s, 1H), 8.14 (m, 3H)

Reference： [1]Patent: EP2116531,2009,A1 .Location in patent: Page/Page column 13-14

30
[ 1202762-79-5 ]
[ 54149-17-6 ]
[ 1202762-95-5 ]

Yield	Reaction Conditions	Operation in experiment
65%	With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2.5h;	A mixture of l-(2-(3-(2-amino-5-chloropyrimidin-4-yl)- lH-indol-5-yl)ethynyl)cyclopentanol (107) (24.6 mg, 0.070 mmol), l-bromo-2-(2- methoxyethoxy)ethane (0.04 mL, 0.21 mmol) and Cs2CO3 ( 45.3 mg, 0.139 mmol) in DMF (5 mL) was heated at 100 0C for 2.5 hrs. After cooled to room temperature, the mixture was diluted with ether, washed with water and brine, dried and concentrated. Purification of the residue by flash chromatography over silica gel, using 4.5:5:0.5 ethyl acetate-hexane-methanol, gave l-(2-(3-(2-amino-5-chloropyrimidin-4-yl)-l-(2-(2-methoxyethoxy)ethyl)-lH-indol-5- yl)ethynyl)cyclopentanol (124) (20.7 mg, 65%): 1H NMR (methanol- d4) delta 8.69(s, 1 H), 8.50(s, 1 H), 8.20(s, 1 H), 7.49 (d, J = 8.0 Hz, 1 H), 7.32(d, J= 8.0 Hz, 1 H), 4.44 (t, J= 5.0 Hz, 2 H), 3.86 (t, J= 5.0 Hz, 2 H), 3.56 (t, J= 5.0 Hz, 2 H), 3.48 (t, J= 5.0 Hz, 2 H), 3.28 (s, 3 H), 2.18- 2.03(m, 4 H), 1.94-1.78(m, 4 H); ms 455.2 (M+H+).

Reference： [1]Patent: WO2009/158011,2009,A1 .Location in patent: Page/Page column 251

31
[ 100511-00-0 ]
[ 54149-17-6 ]
[ 925220-45-7 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1,3-Dihydro-3,3-dimethyl-5-nitro-2H-indol-2-one With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-bromoethyl 2-methoxyethyl ether In N,N-dimethyl-formamide for 3h;	12 Example 12; Synthesis of Compound 51; Compound a (1.0 g) was dissolved in 25 ml of dry DMF, degassed and cooled to 0° C. Sodium hydride (175 mg) was added and the reaction stirred for 30 minutes. 1-bromo-2-(2-methoxyethoxy)ethane (3.26 ml) was added and the reaction stirred for 3 hours. The reaction mixture was poured into 10% citric acid and extracted with ethyl acetate. The organic layer was washed with water, brine, dried, filtered and concentrated to give 1.52 g of crude b which was used without purification.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2007/37791, 2007, A1 Location in patent: Page/Page column 48-49

32
[ 54149-17-6 ]
[ 7463-51-6 ]
[ 883902-92-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate; In N,N-dimethyl-formamide;	Example 1.2.1 4-Bromo-3,5-dimethylphenol (10.05 g, 50.0 mmol) and K2CO3 (9.0 g, 65.2 mmol) were stirred for 10 minutes in DMF (25 mL). <strong>[54149-17-6]1-Bromo-2-(2-methoxyethoxy)ethane</strong> was added, and the reaction mixture was heated at 45 C. overnight under argon. After cooling to room temperature, the reaction mixture was poured into ~300 mL DCM; filtered off white solids. Flash column (silica; 100% hexane) gave 12.95 g (85% yield) of product 5.

Reference： [1]Patent: US2010/308310,2010,A1

33
[ 54149-17-6 ]
[ 107-19-7 ]
[ 89635-79-0 ]

Yield	Reaction Conditions	Operation in experiment
9%		To a stirred suspension of sodium hydride (3.12 g, 78.0 mmol) in THF (100 mL) cooled to 5C in an ice-bath was added a solution of propargyl alcohol (4.60 g, 78.0 mmol) in THF (20 mL) drop-wise. The mixture was stirred at 5C for 30 min and was then allowed to warm to RT and treated dropwise with 1 -bromo-2-(2-methoxyethoxy)ethane (7.00 mL, 52.0 mmol). The reaction mixture was stirred at RT for 16 hr and was then, diluted with water (100 mL) and extracted with diethyl ether (2 x 100 mL). The combined organic extracts were dried, filtered and evaporated in vacuo. The residue was purified by flash column chromatography, eluting with 30% EtOAc in heptane, to afford the title compound (9) (250 mg, 9%) as a colourless oil: 1H NMR (500 MHz, MeOD) delta : 4.18 (2H, d), 3.66-3.69 (2H, m), 3.60-3.66 (4H, m), 3.52-3.56 (2H, m), 3.36 (3H, s), 2.84 (1 H, t).
9%		3-(2-(2-Methoxyethoxy)ethoxy)prop-1-yne (9) To a stirred suspension of sodium hydride (3.12 g, 78.0 mmol) in THF (100 mL) cooled to 5 C. in an ice-bath was added a solution of propargyl alcohol (4.60 g, 78.0 mmol) in THF (20 mL) drop-wise. The mixture was stirred at 5 C. for 30 min and was then allowed to warm to RT and treated dropwise with <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (7.00 mL, 52.0 mmol). The reaction mixture was stirred at RT for 16 hr and was then, diluted with water (100 mL) and extracted with diethyl ether (2*100 mL). The combined organic extracts were dried, filtered and evaporated in vacuo. The residue was purified by flash column chromatography, eluting with 30% EtOAc in heptane, to afford the title compound (9) (250 mg, 9%) as a colourless oil: 1H NMR (500 MHz, MeOD) delta: 4.18 (2H, d), 3.66-3.69 (2H, m), 3.60-3.66 (4H, m), 3.52-3.56 (2H, m), 3.36 (3H, s), 2.84 (1H, t).

Reference： [1]Patent: WO2011/48111,2011,A1 .Location in patent: Page/Page column 44
[2]Patent: US2012/208799,2012,A1 .Location in patent: Page/Page column 21

34
[ 54149-17-6 ]
[ 18158-16-2 ]
[ 1359074-52-4 ]

Yield	Reaction Conditions	Operation in experiment
70%		Step 1: To a solution of benzyl 5-oxo-1,4-diazepane-1-carboxylate (1.0 g, 4 mmol) in DMF (5mL) was added NaH (0.32 g, 13 mmol) and the mixture was stirred at r.t. After 30 min, a solution of <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (1.476g, 8.1mol) in DMF (5ml) was added and the final reaction mixture was stirred at r.t. overnight. The reaction mixture was quenched with water and extracted with EtOAc. The combined organic layers were washed with water (x1), brine (x1), dried over Na2SO4, filtered and solvent was removed under vacuum. Purification by flash column (silica gel) gave 0.98 g (70%) was of the alkylated compound. Step 2: To a solution of the above product (0.7 g, 2 mmol) in MeOH (7 ml) was added Pd/C (70 mg, 10%) and the reaction mixture was stirred at r.t. under hydrogen. After completion of the reaction, the mixture was filtered through celite. Solvent was removed under vacuum to give 350 mg (81%) of 4-(2-(2-methoxyethoxy)ethyl)-1,4-diazepan-5-one.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7155 - 7165

35
[ 20485-44-3 ]
[ 54149-17-6 ]
[ 1774-34-1 ]
[ 1379476-07-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate; In dimethyl sulfoxide;	C. Synthesis of 4,4'-sulfinylbis((2-(2-methoxyethoxy)ethoxy)benzene). 4,4'-sulfinyldiphenol (20.0 g, 85.0 mmol), potassium carbonate (26.6 g, 0.192 mol, 2.26 eq.) and tetramethylethylenediamine (0.495 g, 4.25 mmol, 0.05 eq.) were dissolved in DMSO (100 mL) and stirred at r.t. for 30 minutes. Then <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (32.67 g, 0.179 mmol, 2.1 eq.) was added, the solution heated to 90 C. for 18 h and cooled to r.t. The reaction mixture was diluted with ethyl acetate (600 mL), washed with water (5*500 mL), dried (Na2SO4) and concentrated in vacuo to afford the title compound (33.40 g, 90%) as an orange oil. 1H NMR (acetone-d6) delta: 7.59 (d, J=8.5 Hz, 4H), 7.07 (d, J=8.5 Hz, 4H), 4.17 (t, J=4.5 Hz, 4H), 3.80 (t, J=5 Hz, 4H), 3.63 (t, J=4.5 Hz, 4H), 3.48 (t, J=4.5 Hz, 4H), 3.28 (s, 6H).

Reference： [1]Patent: US2012/141939,2012,A1

36
[ 54149-17-6 ]
[ 79069-15-1 ]
[ 1381872-52-1 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3225 - 3229

37
[ 100-02-7 ]
[ 54149-17-6 ]
[ 69828-74-6 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 10500 - 10504,5
Angewandte Chemie,2012,vol. 124,p. 10652 - 10656,5

38
[ 54149-17-6 ]
[ 1313430-56-6 ]
[ 1429403-80-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate; In N,N-dimethyl-formamide;Schlenk technique;	Under an argon atmosphere, bisimine 11 (3.0 g, 10.12 mmol, 1 eq.), 1-bromo-2-(2-methoxyethoxy) ethane (3.35 mL, 22.26 mmol, 2.2 eq.) of and K2CO3 (5.59 g, 40.48 mmol, 4 eq.) were dissolved in 150 mL of dry DMF in a vacuum dried Schlenk flask. The contents were heated at 100C for 24 hours and the reaction was cooled to room temperature and 200 mL of distilled water was added to it. This was then extracted with EtOAc (3×200 mL) and washed with distilled water (300 mL) and with brine (200 mL). The organic layers were combined and dried over anhydrous Na2SO4 and concentrated in vacuuo to yield a brownish-yellow coloured paste. This paste was thoroughly washed with pentane (3×20 mL) and dried to a yellow powder.

Reference： [1]European Journal of Inorganic Chemistry,2013,p. 54 - 60

39
[ 54149-17-6 ]
[ 1418120-94-1 ]
[ 1448187-22-1 ]

Yield	Reaction Conditions	Operation in experiment
59%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;	(2S,4R)-4-hydroxy-l-(3-(2-(2-methoxyethoxy)ethoxy)benzoyl)-N-(4-(4-methylthiazol-5- yl)benzyI)pyrrolidine-2-carboxamide A mixture of (2S,4R)-4-hydroxy-l-(3-hydroxybenzoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide (55 mg, 0.13 mmol) and potassium carbonate (55 mg, 0.40 mmol) in DMF (0.8 mL) was treated with l-bromo-2-(2-methoxyethoxy)ethane (commercially available from for example Aldrich) (0.034 mL, 0.25 mmol) and the reaction stirred at 50C for 2.5 hours. Additional l-bromo-2-(2-methoxyethoxy)ethane (0.034 mL, 0.25 mmol) was added and the mixture stirred at 50C overnight. The product was subjected to purification by mass-directed automated preparative HPLC (formic acid modifier) to afford the title compound (40 mg, 0.074 mmol, 59 % yield) LCMS RT= 0.74 min, ES+ve m/z 540 [M+H]+.
59%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;	A mixture of (2S,4R)-4-hydroxy-1-(3-hydroxybenzoyl)-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (55 mg, 0.13 mmol) and potassium carbonate (55 mg, 0.40 mmol) in DMF (0.8 mL) was treated with <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (commercially available from for example Aldrich) (0.034 mL, 0.25 mmol) and the reaction stirred at 50 C. for 2.5 hours. Additional <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (0.034 mL, 0.25 mmol) was added and the mixture stirred at 50 C. overnight. The product was subjected to purification by mass-directed automated preparative HPLC (formic acid modifier) to afford the title compound (40 mg, 0.074 mmol, 59% yield) LCMS RT=0.74 min, ES+ve m/z 540 [M+H]+.

Reference： [1]Patent: WO2013/106646,2013,A2 .Location in patent: Page/Page column 164
[2]Patent: US2014/356322,2014,A1 .Location in patent: Paragraph 0383

40
[ 54149-17-6 ]
(S)-methyl 2-(3-hydroxypyrrolidin-1-yl)-5-(trifluoromethyl)benzoate [ No CAS ]
(S)-methyl 2-(3-(2-(2-methoxyethoxy)ethoxy)-pyrrolidin-1-yl)-5-(trifluoromethyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		General procedure: To a solution of 11b (1.50 g, 5.18 mmol) in DMF (20 mL) was added NaH (60% in mineral oil w/w, 0.23 g, 5.75 mmol) in small portions at 0 C. The reaction mixture was stirred at 0 C for 1 h, 2-cyclopropylethyl 4-methylbenzenesulfonate, (1.60 g, 6.65 mmol) was added; stirring was continued for 18 h and then heated at 50 C for 4 h. The reaction mixture was quenched by addition of aqueous saturated NH4Cl solution (10 mL) at 0 C and extracted with ethyl acetate (100 mL x 3), washed with water and brine' dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, the residue was subjected to column chromatography with a gradient of 10-30% EtOAc in hexanes to give 11c as a colorless oil (1.76 g, 95%). 1H NMR (300 MHz, CDCl3) delta 7.83-7.79 (m, 1H), 7.50-7.45 (m, 1H), 6.80-6.75 (m, 1H), 4.14-4.08 (m, 1H), 3.88 (s, 3H), 3.58-3.38 (m, 4H), 3.36-3.28 (m, 1H), 3.08-3.00 (m, 1H), 2.16-2.00 (m, 2H), 1.43-1.35 (m, 2H), 0.69-0.59 (m, 1H), 0.41-0.35 (m, 2H), 0.19-0.03 (m, 2H); MS (ES+) m/z 358.1 (M+1).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 7724 - 7734

41
[ 54149-17-6 ]
[ 1536312-09-0 ]
[ 1610450-27-5 ]

Yield	Reaction Conditions	Operation in experiment
380 mg	With sodium hydride; sodium iodide; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 3.5h;Inert atmosphere;	(ii) (3-Methoxy-5-nitrophenyl)(2-(2-(2-methoxyethoxy)ethoxy)ethyl)sulfane The product from step (i) above (524 mg, 2.286 mmol) was dissolved in dry DMF (10 mL) under N2 and NaH (96 mg, 2.400 mmol, 60% wt) added. Stirred for 10 min then 1- bromo-2-(2-methoxyethoxy)ethane (323 muIota_, 2.400 mmol) and Nal (34.3 mg, 0.229 mmol) added. Stirred at rt for 2.5h, charged again with NaH (96 mg, 2.400 mmol) and 1-bromo- 2-(2-methoxyethoxy)ethane (323 muIota_, 2.400 mmol) and stirred for a further 1 h. The mixture was partitioned between NH4CI solution (20 mL) and ethyl acetate (20 mL). Organic layer was separated, washed with 20% NaCI solution. (20 mL), dried (MgS04), filtered and solvent evaporated. The crude product was purified by chromatography on silica gel (40 g column, 30% EtOAc:isohexane to 50%) to afford the sub-title compound (380 mg) as a clear yellow oil. 1 H NMR (400 MHz, CDCI3) delta 7.78 (t, 1 H), 7.51 (t, 1 H), 7.16 (dd, 1 H), 3.88 (s, 3H), 3.73 (t, 2H), 3.68 - 3.61 (m, 6H), 3.59 - 3.51 (m, 2H), 3.38 (s, 3H), 3.20 (t, 2H).
1 g		The product from step (ii) above (1 g, 4.36 mmol) was dissolved in dry DMF (10 mL) under nitrogen and NaH (0.2 g, 5.00 mmol) added. Stirred for 10 minutes, then <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (0.75 ml, 5.57 mmol) and NaI (0.065 g, 0.436 mmol) added and stirred at rt for 2.5 h. The mixture was charged again with NaH (0.2 g, 5.00 mmol) and <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (0.75 ml, 5.57 mmol), stirred for a further 1 h then partitioned between NH4Cl solution (200 mL) and ethyl acetate (100 mL). The organic layer was separated and washed with 20% NaCl soln. (200 mL). The organic layer was separated, dried (MgSO4), filtered and solvent evaporated. The crude product was purified by chromatography on silica gel (80 g column, 30% EtOAc:isohexane to 50%) to afford the sub-title compound (1 g) as a clear yellow oil. 1H NMR (400 MHz, CDCl3) delta 7.80 (t, 1H), 7.53 (t, 1H), 7.18 (dd, 1H), 3.89 (s, 3H), 3.75 (t, 2H), 3.71-3.63 (m, 6H), 3.59-3.53 (m, 2H), 3.40 (s, 3H), 3.22 (t, 2H).
1 g		The product from step (ii) above (ig, 4.36 mmol) was dissolved in dry DMF (10 mL) undernitrogen and NaH (0.2 g, 5.00 mmol) added. Stirred for 10 minutes, then <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (0.75 ml, 5.57 mmol) and Nal (0.065 g, 0.436 mmol) added and stirred at rt for 2.5 h. The mixture was charged again with NaH (0.2 g, 5.00 mmol) and 1- bromo-2-(2-methoxyethoxy)ethane (0.75 ml, 5.57 mmol), stirred for a further 1 h then partitioned between NH4CI solution (200 mL) and ethyl acetate (100 mL). The organic layerwas separated and washed with 20% NaCI soln. (200 mL). The organic layer was separated, dried (Mg504), filtered and solvent evaporated. The crude product was purified by chromatography on silica gel (80 g column, 30% EtOAc:isohexane to 50%) to afford the sub-title compound (1 g) as a clear yellow oil.1H NMR (400 MHz, CDCI3) O 7.80 (t, 1H), 7.53 (t, 1H), 7.18 (dd, 1H), 3.89 (5, 3H), 3.75 (t,2H), 3.71 - 3.63 (m, 6H), 3.59 - 3.53 (m, 2H), 3.40 (5, 3H), 3.22 (t, 2H).

Reference： [1]Patent: WO2014/76484,2014,A1 .Location in patent: Page/Page column 73; 74; 80
[2]Patent: US2014/296208,2014,A1 .Location in patent: Paragraph 1460; 1461
[3]Patent: WO2014/162126,2014,A1 .Location in patent: Page/Page column 165

42
[ 1991-52-2 ]
[ 54149-17-6 ]
1-[2-(2-methoxyethoxy)ethoxy]-4-methoxy-2,5-di-tert-butylbenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃;	Scheme 2 is an illustration of the synthesis of the title compound. 2,5-di-tert-butyl-4-methoxyphenol (9 mmol) was dissolved in anhydrous N,N-dimethylformamide (10 ml). Cesium carbonate (13 mmol) and <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (9 mmol) was added to the solution. The reaction mixture was then stirred at room temperature overnight. After removal of the solvent, the residue was partitioned between dichloromethane (DCM) and aqueous NaHCO3 (0.1 M). The organic portion was separated and dried over Na2SO4 and then the solvent was removed under vacuum. The crude product was chromatographed (silica, hexanes/DCM from 5:1 to 1:1) to provide pure 1-methoxy-4-[2-(2-methoxyethoxy)ethoxy]-2,5-di-tert-butyl-benzene in an 87% yield. 1H NMR (300 MHz, CDCl3): delta/ppm 6.83 (s, 1H), 6.82 (s, 1H), 4.14 (t, J=4.5 Hz, 2H), 3.89 (t, J=4.5 Hz, 2H), 3.80 (s, 3H), 3.72 (t, J=4.5 Hz, 2H), 3.58 (t, J=4.5 Hz, 2H), 3.40 (s, 3H), 1.38 (s, 9H)), and 1.35 (s, 9H). The purity was over 99.5% based GC-mass spectroscopy, and the molecular weight was observed at 338.3, which is consistent with the theoretical value, 338.5. Cyclic voltammograms were recorded for a solution of 0.01M 1-methoxy-4-[2-(2-methoxyethoxy)ethoxy]-2,5-di-tert-butyl-benzene in an electrolyte of 1.2M LiPF6 in EC/EMC (3:7 by weight), using a Pt/Li/Li three-electrode system at various scan rates. See FIG. 6. The reversible electrochemical reaction at 3.8-4.1 V vs. Li/Li+is assigned to the redox reaction of the exemplary electrolyte solvent. Voltage profiles overcharge test of a MCMB/LFP cell containing 0.4 M 1-methoxy-4-[2-(2-methoxyethoxy)ethoxy]-2,5-di-tert-butyl-benzene in 1.2M LiPF6 in EC/EMC (3:7 by weight) were recorded over the course of 0-200 h. See FIG. 7. The charging rate was at C/2 and the overcharge was 100%. The electrolyte was observed to provide high rate overcharge protection at C/2 charging rate. Capacity retention profiles of MCMB/LiFePO4 cell containing 0.4 M 1-methoxy-4-[2-(2-methoxyethoxy)ethoxy]-2,5-di-tert-butyl-benzene in 1.2M LiPF6 in EC/EMC (3:7 by weight) were recorded. See FIG. 8. The charging rate was at C/2 and the overcharge was 100%. Under these condition, the cells were observed to survive about 40 overcharge test cycles. Capacity retention profiles of LFP/LTO cells using an electrolyte of 2:1 [1,2M LiPF6 in EC/EMC (3:7 by weight)] to [1-methoxy-4-[2-(2-methoxyethoxy)ethoxy]-2,5-di-tert-butyl-benzene] by weight were recorded. See FIG. 9. The cells were cycled at room temperature from 1.5 V to 2.1V at C/10 rate. Despite the degradation of the capacity, the cycle performance clearly indicated that 1-methoxy-4-[2-(2-methoxyethoxy)ethoxy]-2,5-di-tert-butyl-benzene can be used as co-solvent in the electrolyte system.

Reference： [1]Patent: US2014/255793,2014,A1 .Location in patent: Paragraph 0091 - 0096

43
[ 54149-17-6 ]
(2S,6R,11R)-8-(aminomethyl)-3-(cyclopropylmethyl)-6,11-dimethyl-3,4,5,6-tetrahydro-2,6-methanobenzo[d]azocin-1(2H)-one [ No CAS ]
(2S,6R,11R)-3-(cyclopropylmethyl)-8-(((2-(2-methoxyethoxy)ethyl)amino)methyl)-6,11-dimethyl-3,4,5,6-tetrahydro-2,6-methanobenzo[d]azocin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 20h;	(2S,6R,l lR)-8-(aminomethyl)-3-(cyclopropylmethyl)-6,l l -dimethyl-3,4,5,6-tetra^ methanobenzo[d]azocin-l(2H)-one (160 mg, 0.54 mmol) prepared in a manner similar to Example 17, stepl, and mPEGi-Br (981 mg, 5.4 mmol) was dissolved in 1.6 mL of DMF. NaOH (214 mg, 5.4 mmol) was added to the above mixture and reaction was stirred for 20 h at room temperature. Reaction mixture was filtered and concentrated under vacuum to get a residue. Residue was purified by column chromatography to yield (2S,6R,1 lR)-3- (cyclopropylmethyl)-8-(((2-(2-methoxyethoxy) ethyl)amino)methyl)-6,l l -dimethyl-3 ,4,5,6- tetrahydro-2,6-methanobenzo [d]azocin-l (2H)-one (18) as gummy oil (110 mg, 51% yield). H NMR (500 MHz, CDC13): delta 7.95 (d, 1H), 7.3 (m, 2H),3.88 (s, 2H), 3.6-3.7 (m, 4H), 3.52- 3.55 (m, 2H),3.37 (s, 3H), 3.3 (m, 1 H),2.92 (m, IE), 2.85 (m, lH), 2.91-2.94 (m, 1 H), 2.72- 2.76 (m, 1 H),1.97-2.13 (m, 4H), 1.34 (s, 3H), 1.25 (m, 1H), 0.88-0.90 (m, 4H), 0.46-0.48 (m, 2H), 0.26 (m,lH),0.04- 0.07 (m, 1H), MS (ESI) for C24H36N203: 401.2616 (MH+). The free base was dissolved in 4M hydrochloride in 2-propanol. The mixture was concentrated to afford product as hydrochloride salt.

Reference： [1]Patent: WO2015/79459,2015,A1 .Location in patent: Paragraph 00272

44
[ 54149-17-6 ]
(2S,6R,11R)-6,11-dimethyl-1-oxo-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-yl trifluoromethanesulfonate hydrochloride [ No CAS ]
(2S,6R,11R)-8-hydroxy-3-(2-(2-methoxyethoxy)ethyl)-6,11-dimethyl-3,4,5,6-tetrahydro-2,6-methanobenzo[d]azocin-1(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With caesium carbonate; In acetonitrile; at 75℃; for 16h;	(2S,6R, I lR)-6,l l -dimethyl-l-oxo- l ,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-y trifluoromethanesulfonate hydrochloride (120 mg, 0.33 mmol), Cs2C03 (214.9 mg, 0.6494 mmol) and mPEG2-Br (78.45 mg, 0.4286 mmol) were dissolved in acetonitrile. The mixture was heated to 75 C for 16 h and cooled to room temperature. The mixture was concentrated under vacuum and purified by flash chromatography to yield (2S,6R,l lR)-8-hydroxy-3-(2- (2-methoxyethoxy) ethyl)-6,l l-dimethyl-3,4,5,6-tetrahydro-2,6-methanobenzo[d]azocin- l(2H)-one (14) (51.5 mg, 47% yield). NMR (500 MHz, CDC13): delta 8.02 (d, 1 H), 6.85 (m, 2H), 4.21-4.23 (m, 2H), 3.89 (t, 2H), 3.57-3.59 (m, 2H), 3.39 (s, 3H), 3.27 (d, 1H), 2.72-2.75 (m, 1 H), 2.55-2.61 (m, 1 H), 2.08-2.13 (m, 1H), 1.87-1.94 (m, 1H), 1.45-1.48 (m, 1H), 1.41 (s, 3H), 0.85 (d, 3H); MS (ESI) for C19H27N04: 334.1965 (MH+). The free base was dissolved in 4M hydrochloride in 2-propanol. The mixture was concentrated to afford product as hydrochloride salt.

Reference： [1]Patent: WO2015/79459,2015,A1 .Location in patent: Paragraph 00256

45
[ 389-58-2 ]
[ 54149-17-6 ]
4,4-bis[2-(2-methoxyethoxy)ethyl]-4H-cyclopenta[2,1-b;3,4-b']dithiophene [ No CAS ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 14115 - 14118

46
[ 137-00-8 ]
[ 54149-17-6 ]
5-{2-[2-(2-methoxyethoxy)ethoxy]ethyl}-4-methylthiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%		General procedure: To a stirred solution of sodium hydride (60% dispersion in mineral oil) ( 882 mg, 22.05 mmol) in anhydrous DMF (50 ml) a solution of 4-methyl-5-thiazole ethanol (900 mg, 6.28 mmol) in anhydrous DMF (15 ml) was added at room temperature. After stirring for 90 min., 1-bromo-2-methoxyethane (3.5 g, 25.2 mmol) in anhydrous DMF (20 ml) was added dropwise at 0oC. After stirring the mixture at room temperature overnight, H2O (15 ml) was slowly added. The solvent was evaporated under reduced pressure and H2O (50 ml) was added to the residue. The aqueous phase was extracted with AcOEt (3 times) and the combined organic phases were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography (hexane/AcOEtmixtures) to afford 2 (949 mg, 75%) as a yellow oil.

Reference： [1]Tetrahedron Letters,2016,vol. 57,p. 3291 - 3293

47
[ 54149-17-6 ]
[ 62-53-3 ]
[ 484679-02-9 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 80℃; for 24h;	Aniline (1.61g, 17.3mmol), potassium carbonate (9.56g, 69.2mmol), potassium iodide (1.43g,8.65mmol) and 1bromo2(2methoxyethoxy)ethane (9 .50g, was suspended 51.9 mmol) in dry DMF (5.0mL), it washeated at 80 C 24 hours. After allowed to cool to room temperature, ethyl acetate (200 mL) was added and the aqueouswas washed successively with saturated brine. The organic phase was dried over anhydrous magnesium sulfate, and thefiltrate was concentrated under reduced pressure. Crude was purified by silica gel column chromatography to give 4.27g ofcompound 14 as a colorless oily substance. 83% yield.

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 5708 - 5712
Angew. Chem.,2016,vol. 128,p. 5802 - 5806,5
[2]Patent: JP2016/196447,2016,A .Location in patent: Paragraph 0074-0076

48
[ 54149-17-6 ]
[ 39630-68-7 ]
C₁₇H₂₄O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate In acetone for 12h; Reflux;	3 Etherification of Compound 1 Etherification of Compound 1: 1 was added to the flask three Ommo a compound l (2.38g), acetone (100mL), lOmmol potassium carbonate (1 · 37g), the compound lOmmol Br (CH2CH20) 2CH3 (l .81g), heating after the reaction was refluxed for 2 hours, concentrated to give crude product was isolated by column chromatography, eluting with dichloromethane / petroleum ether (volume ratio 3: 1) mixture as an eluent, the solvent rotary evaporated to give a white solid compound 2 (2.13g, yield : 71.0%).

Reference： [1]Current Patent Assignee: NATIONAL CENTER FOR NANOSCIENCE AND TECHNOLOGY - CN103922915, 2016, B Location in patent: Paragraph 0097-0099

49
[ 54149-17-6 ]
[ 1951-36-6 ]
[ 1628897-24-4 ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 10922 - 10929

50
[ 98-00-0 ]
[ 54149-17-6 ]
2-(2,5,8-trioxa-nonyl-1-yl)furan [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.7%	With sodium hydride; In tetrahydrofuran;	Step 1: Preparation of 2-(2,5,8-trioxa-nonyl-1-yl) furan To a solution formed by furfuralcohol (2.0 g, 20.4 mmol) dissolved in tetrahydrofuran (100 mL) NaH (1.5 g, 61.3 mmol) was added, followed by the addition of <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (7.5 g, 40.8 mmol), and the reaction liquid was stirred overnight. The reaction mixture was extracted with ethyl acetate, and the extract was washed with distilled water, dried with anhydrous sodium sulfate, concentrated to dryness under reduced pressure, the residue was purified by a silica gel column to give 3.5 g of a pale yellow oil with a yield of 85.7%. MS Detection: MASS(ESI+) m/z=223.1 (M+Na)+.

Reference： [1]Patent: US2016/272604,2016,A1 .Location in patent: Paragraph 0074; 0075; 0076; 0077

51
[ 591-20-8 ]
[ 54149-17-6 ]
1-bromo-3-(2-(2-methoxyethoxy)ethoxy)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;	Example 34 Preparation of N-{3-[2-(2-methoxyethoxy)ethoxy]phenyl}-17-methylmorphinan-3-amine (34), hydrochloride salt Step 1. Synthesis of l-bromo-3-(2-(2-methoxyethoxy)ethoxy)benzene, A mixture of 3-bromophenol (0.3271g, 1.891 mmol), l-bromo-2-(2- methoxyethoxy)ethane (0.28 mL, 2.080 mmol), and potassium carbonate (0.784g, 5.67 mmol) in dimethyl formamide (5 mL) was stirred at 60 C overnight. The reaction mixture was poured into 20 mL of 5% LiCl solution and extracted with ethyl acetate 3x30mL. The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated. After drying under high vacuum, the pure product was obtained as colorless oil in quantitative yield. 1H NMR (400 MHz, CDC13): delta 7.12 (d, 1H), 7.08 (d, 2H), 6.84 (tt, 1H), 4.11 (t, 2 H), 3.85 (t, 2H), 3.71 (t, 2H), 3.57 (t, 2H), 3.39 (s, 3H). MS (EI) for CnHi5Br03: 292 (MNH4+).

Reference： [1]Patent: WO2016/182840,2016,A1 .Location in patent: Paragraph 00303-00304

52
[ 95-56-7 ]
[ 54149-17-6 ]
[ 929259-36-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;	Example 35 Preparation of N-{2-[2-(2-methoxyethoxy)ethoxy]phenyl}-17-methylmorphinan-3-amine (35), hydrochloride salt (35) Step 1. Synthesis of l-bromo-2-(2-(2-methoxyethoxy)ethoxy)benzene, A mixture of 2-bromophenol (0.448g, 2.59 mmol), l-bromo-2-(2- methoxyethoxy)ethane (0.383mL, 2.85 mmol), and potassium carbonate (1.073g, 7.76 mmol) in dimethyl formamide (5 mL) was stirred at 60 C overnight. The reaction mixture was poured into 20 mL of 5% LiCl solution and extracted with ethyl acetate 3x30mL. The organic layer was washed with brine, was dried over sodium sulfate, was filtered and was concentrated. After drying under high vacuum, the pure product was obtained as colorless oil (656.7 mg) in 92% yield. *Eta NMR (400 MHz, CDCl-3): delta 7.54 (d, 1H), 7.24 (t, 1H), 6.92 (d, 1H), 6.83 (t, 1H), 4.40 (t, 2 H), 3.92 (t, 2H), 3.80 (t, 2H), 3.58 (t, 2H), 3.39 (s, 3H). MS (EI) for CnHi5Br03: 292 (MNH4+).

Reference： [1]Patent: WO2016/182840,2016,A1 .Location in patent: Paragraph 00306-00307

53
[ 54149-17-6 ]
17-methylmorphinan-3-yl trifluoromethanesulfonate [ No CAS ]
17-[2-(2-methoxyethoxy)ethyl]morphinan-3-yl trifluoromethanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With caesium carbonate; In acetonitrile; at 50℃; for 18h;	Example 83 Preparation of 17-[2-(2-methoxyethoxy)ethyl]-N-(pyridin-3-yl)morphinan-3-amine (83), hydrochloride salt Step 1 : Preparation of 17-[2-(2-etaiotabeta1iotaomicronchigamma61iotaomicronchinu)61iotagamma1]etaiotaomicronphi1iotaeta3eta-3-gamma1 trifluoromethanesulfonate, The acetonitrile solution of morphinan-3-yl trifluoromethanesulfonate (2.7 g, 7.19 mmol), l-bromo-2-(2-methoxyethoxy)ethane (2.6 g, 14.4 mmol) and cesium carbonate (2.6 g, 43.2 mmol) was heated at 50 C for 18 hours. After cooling the mixture to room temperature, all solvent was removed and the reaction mixture was extracted with dichloromethane twice. The solvent was evaporated and the residue was purified by silica gel chromatography using Biotage with dichloromethane/methanol eluents. 17-[2-(2- Methoxyethoxy)ethyl]morphinan-3-yl trifluoromethanesulfonate was obtained as a light- yellow liquid (2.5 g, 73% yield), MS (EI) for C22H30F3NO5S: 478.2 (MH+).

Reference： [1]Patent: WO2016/182840,2016,A1 .Location in patent: Paragraph 00428-00429

54
[ 74115-13-2 ]
[ 54149-17-6 ]
[ 1364125-18-7 ]

Yield	Reaction Conditions	Operation in experiment
52.1%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h;Microwave irradiation;	Example 48 Preparation of N-{5-[2-(2-methoxyethoxy)ethoxy]pyridin-3-yl}-17-methylmorphinan-3- amine (48), hydrochloride salt Step 1. Synthesis of 3-bromo-5-(2-(2-methoxyethoxy)ethoxy)pyridine, A mixture of 5-bromopyridin-3-ol (100 mg, 0.575 mmol), l-bromo-2-(2- methoxyethoxy)ethane (105 mg, 0.575 mmol) and K2C03 (159 mg, 1.149 mmol) in DMF (3 mL) was irradiated in a microwave at 80 C for two hours. The reaction mixture was cooled to room temperature and poured into 15 mL of ethyl acetate and IN NaOH (20 mL). The organic layer was washed with brine (20 mL), dried over anhydrous sodium sulfate, was filtered and was concentrated. The crude product was purified by flash column chromatography on silica gel to afford 3-bromo-5-(2-(2-methoxyethoxy)ethoxy)pyridine (82.7 mg, 52.1%). MS (EI) for Ci0Hi4BrNO3: 277.8 (MH+)

Reference： [1]Patent: WO2016/182840,2016,A1 .Location in patent: Paragraph 00333-00334

55
[ 54149-17-6 ]
[ 96630-88-5 ]
4-chloro-3-(2-(2-methoxyethoxy)ethoxy)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48.9%	With caesium carbonate; In N,N-dimethyl acetamide; at 120℃; for 2.0h;Microwave irradiation;	Example 66 Preparation of (4bR,8aR,9R)-N-(3-(2-(2-methoxyethoxy)ethoxy)pyridin-4-yl)-ll- methyl-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthren-3-amine (66), hydrochloride salt Step 1. Synthesis of 4-chloro-3-(2-(2-methoxyethoxy)ethoxy)pyridine, A mixture of <strong>[96630-88-5]4-chloropyridin-3-ol</strong> (100 mg, 0.772 mmol), l-bromo-2-(2- methoxyethoxy)ethane (141 mg, 0.772 mmol) and CS2CO3 (503 mg, 1.544 mmol) in dimethylacetamide (5 mL) was irradiated in a microwave at 120 C for two hours. The reaction mixture was cooled to room temperature and poured into 20 mL of water. The aqueous solution was extracted with ethyl acetate 3x20 mL. The organic layer was combined, was washed with brine (50 mL), was dried over anhydrous sodium sulfate, was filtered and was concentrated. The crude product was purified via flash column chromatography on silica gel to afford 4-chloro-3-(2-(2-methoxyethoxy)ethoxy pyridine (87.4 mg, 48.9%). MS (EI) for C10H14CINO3: 232.0 (MH+).

Reference： [1]Patent: WO2016/182840,2016,A1 .Location in patent: Paragraph 00370-00371

56
[ 54149-17-6 ]
[ 108-44-1 ]
N-(2-(2-methoxyethoxy)ethyl)-3-methylaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 100℃; for 4h;	To a solution of m-toluidine (lOg, 9.3mmol) in DMF (lOmL), 1-bromo-2-(2- methoxyethoxy)ethane (0.85g, 4.6mmol) and diisopropylamine (1.2g, 0.93mmol) was added. The mixture was heated to 100C for 4h. The mixture was diluted with ethyl acetate and water, and the layers were separated. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was then concentrated. The residue was purified by column chromatography (silica, heptane/ethyl acetate) to afford the desired product (650mg, 66%) as an oil. ?H NMR (300 MHz, CDC13) oe 7.07 (t, J 7.5, 1H), 6.56 (d, J 7.5, 1H), 6.52 - 6.45 (m, 2H), 3.71 (t, J= 5.3, 2H), 3.67 - 3.62 (m, 2H), 3.60 - 3.52 (m, 2H), 3.31 (t, J= 5.3, 2H), 2.28 (s, 3H); ESI MS m/z 210 [M + Hj.

Reference： [1]Patent: WO2016/210294,2016,A1 .Location in patent: Paragraph 00318

57
[ 54149-17-6 ]
[ 100-83-4 ]
[ 64994-51-0 ]

Yield	Reaction Conditions	Operation in experiment
79%		A solution of 3-hydroxybenzaldehyde (1.00 g, 8.18 mmol) and K2CO3 (1.13 g, 8.18 mmol) dissolved in anhydrous DMF (25 mL) was heated to 80 & lt; 0 & gt; C for 30 min. After addition of l-bromo-2- (2-methoxyethoxy) ethane (3.31 mL, 24.6 mmol), the reaction mixture was stirred at room temperature for additional 6 h. The solvent was removed under reduced pressure to give a crude product dissolved in ethyl acetate. The solution was treated with aqueous NH4Cl and extracted with ethyl acetate. The collected organic layer was washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo. The crude residue was purified by flash column chromatography (EA: Hex = 1: 4) using silica gel to obtain the desired compound (1.45 g, 79%).

Reference： [1]Patent: KR101672829,2016,B1 .Location in patent: Paragraph 0293-0296

58
[ 54149-17-6 ]
[ 100-83-4 ]
3-(2-(2-methoxyethoxy)ethoxy)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		A solution of 3-hydroxybenzaldehyde (1.00 g, 8.18 mmol) and K2CO3 (1.13 g, 8.18 mmol) dissolved in anhydrous DMF (25 mL) was heated to 80 & lt; 0 & gt; C for 30 min. After addition of l-bromo-2- (2-methoxyethoxy) ethane (3.31 mL, 24.6 mmol), the reaction mixture was stirred at room temperature for an additional 12 h. The solvent was removed under reduced pressure to give a crude product dissolved in ethyl acetate. The solution was treated with aqueous NH4Cl and extracted with ethyl acetate. The collected organic layer was washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo. The crude residue was purified by flash column chromatography (EA: Hex = 1: 4) using silica gel to obtain the desired compound (1.47 g, 80%)

Reference： [1]Patent: KR101672829,2016,B1 .Location in patent: Paragraph 0310-0313

59
[ 123-75-1 ]
[ 54149-17-6 ]
1-(2-(2-methoxyethoxy)ethyl)pyrrolidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%		Under an argon atmosphere, sodium hydride (2.41g, 100 mmol) was suspended in THF (20 mL). Pyrrolidine (3.50 g, 50 mmol) dissolved in 30 mL of THF was added dropwise to the solution. The mixture was stirred at 25C for 15 h, then <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (9.15 g, 50 mmol) was added to the solution. After stirring at 70C for 15 h, the resulting suspension was filtered to remove the white precipitate. The solvent was removed from the filtrate by rotary evaporation to give the yellow crude product. The crude product was purified by distillation under reduced pressure. The fraction collected at 120C under a reduced pressure of 1 mm Hg afforded the pyrrolidine derivative 1-(2-(2-methoxyethoxy)ethyl)pyrrolidine (OE2py) as a colorless oil (yield=6.16 g, 72%). 1H NMR (CDCl3 relative to tetramethylsilane (TMS), 300 MHz): delta (ppm)=3.41 (m, 6H), 3.38 (s, 3H), 2.69 (t, J=5.2Hz, 2H), 2.55 (t, J=5.1Hz, 4H), 1.76 (m, 4H). MS (FAB+): m/z=174.2.

Reference： [1]Electrochimica Acta,2017,vol. 241,p. 272 - 280

60
[ 54149-17-6 ]
[ 95-01-2 ]
[ 1172635-12-9 ]

Yield	Reaction Conditions	Operation in experiment
36.4%	With 18-crown-6 ether; potassium carbonate; In acetone; at 80℃;	In scintillation vial, a suspension of 2,4-dihydroxybenzaldehyde (0.552 g, 4 mmol), K2CO3 (0.552 g, 4.0 mmol), 18-crown-6 (0.106 g, 0.4 mmol) and 1-bromo-2-(2-methoxyethoxy) ethane (90-95% purity, 0.61 g, 3.0 mmol) in acetone (5 ml) was heated and stirred overnight at 80 C. The reaction mixture was cooled to room temperature, acidified with HCl, aq. 1M and extracted with ethyl acetate (25 ml). Organic layer was washed with water (25 ml) and then with brine (25 ml). Organic layer was dried over MgSO4, concentrated and chromatographed to yield compound 61a (0.35 g, 1.46 mmol, 36.4%).
0.35 g	With 18-crown-6 ether; potassium carbonate; In acetone; at 80℃;	In scintillation vial, a suspension of 2,4-dihydroxybenzaldehyde (0.552 g, 4 mmol), K2CO3 (0.552 g, 4.0 mmol), 18-crown-6 (0.106 g, 0.4 mmol) and 1-bromo-2-(2-methoxyethoxy) ethane (90-95% purity, 0.61 g, 3.0 mmol) in acetone (5 ml) was heated and stirred overnight at 80 C. The reaction mixture was cooled to room temperature, acidified with HCl, aq. 1M and extracted with ethyl acetate (25 ml). Organic layer was washed with water (25 ml) and then with brine (25 ml). Organic layer was dried over MgSO4, concentrated and chromatographed to yield compound 61a (0.35 g, 1.46 mmol, 36.4%).

Reference： [1]Patent: US2017/182051,2017,A1 .Location in patent: Paragraph 0181
[2]Patent: US2019/851,2019,A1 .Location in patent: Paragraph 0491

61
[ 54149-17-6 ]
[ 4498-68-4 ]
ethyl 1-(2-(2-methoxyethoxy)ethyl)-3a,7a-dihydro-1H-indazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40.5%	With caesium carbonate; In acetonitrile; at 80℃;	To a vial containing ethyl 1H-indazoie-3-carboxyiate (150 mg, 0.789 inmol) in C1-I3CN (3 mL), were added I -bromo-2-(2-methoxyethoxy)etharie (217 mg, 1.183 mniol) and Cs?C03 (385 mg, 1.183 mrnol). The vial was sealed and the mixture was stirred at 80C overnight. Afterwards, water was added, extracted with EtOAc, washed organic layer with 10% LiCI, brine, concentrated and the residue was purified by normal phase chromatography with the second peak to elute off column being the desired product (105mg, 40.5%). MS (ESI) m/?: 293.2 (M±HY?. ?H NMR (400MHz, CDCI3) 5 8.20 (dt, J::r8.2,1.0 Hz, IH), 7.63- 7.57(m, 1H), 7.42 (ddd, J=8.4, 7.0, 1.1 Hz, IH), 7.30 (ddd, J=8.1,7.0, 0.9 Hz, 1H), 4.67 (t, J=5.6 Hz, 2H), 4.53 (q, J:::73 Hz, 21-1), 3.97 (t, J:::57 Hz. 21-1),3.56 - 3.48 (rn, 2H). 343 - 337 (m, 2H), 3.28 (s, 31:1), 1.48 (t, J:::7.2 Hz,3H).

Reference： [1]Patent: WO2017/123860,2017,A1 .Location in patent: Page/Page column 189; 190

62
[ 54149-17-6 ]
[ 4498-68-4 ]
1-(2-(2-methoxyethoxy)ethyl)-3a,7a-dihydro-1H-indazole-3-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2017/123860,2017,A1

63
[ 54149-17-6 ]
[ 374898-86-9 ]
2-(2-methoxyethoxy)ethyl 3β,28-diacetoxy-18-oxo-19,20,21,29,30-pentanorlupan-22-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With silver carbonate; In N,N-dimethyl-formamide; at 20℃; for 72h;	General procedure: Silver carbonate (220mg; 800mumol) was added to the solution of acid 5 (200mg; 400mumol) in dry DMF (10.0mL) Then 1-bromo-2-methoxyethane (60mul; 800mumol) was added and the reaction mixture was stirred for 3 days at r.t. Work-up (A), column chromatography on silica gel and crystallization afforded final products 5a and 5b.

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 140,p. 403 - 420

64
[ 54149-17-6 ]
[ 472-15-1 ]
2-(2-methoxyethoxy)ethyl 3β-hydroxylup-20(29)-en-28-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; acetonitrile; at 20℃; for 48h;	General procedure: DBU (4.5mmol) and 1-bromo-2-methoxyethane or 1-(2?-methoxyethoxy)-2-bromoethane were added to a solution of a triterpenic acid 1, 2, 3, 4 (2.2mmol) in the mixture of CH2Cl2 (6mL) and MeCN (2mL). The reaction mixture was stirred for 2 days at room temperature. The work-up (A), column chromatography on silica gel, and crystallization afforded final products 1a - 3a and 1b - 3b.

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 140,p. 403 - 420

65
[ 54149-17-6 ]
[ 38736-78-6 ]
2-(2-methoxyethoxy)ethyl 3β-hydroxylup-28-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; acetonitrile; at 20℃; for 48h;	General procedure: DBU (4.5mmol) and 1-bromo-2-methoxyethane or 1-(2?-methoxyethoxy)-2-bromoethane were added to a solution of a triterpenic acid 1, 2, 3, 4 (2.2mmol) in the mixture of CH2Cl2 (6mL) and MeCN (2mL). The reaction mixture was stirred for 2 days at room temperature. The work-up (A), column chromatography on silica gel, and crystallization afforded final products 1a - 3a and 1b - 3b.

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 140,p. 403 - 420

66
[ 54149-17-6 ]
[ 374901-99-2 ]
2-(2-methoxyethoxy)ethyl 3β-acetoxy-21-oxolup-18-en-28-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; acetonitrile; at 20℃; for 48h;	General procedure: DBU (4.5mmol) and 1-bromo-2-methoxyethane or 1-(2?-methoxyethoxy)-2-bromoethane were added to a solution of a triterpenic acid 1, 2, 3, 4 (2.2mmol) in the mixture of CH2Cl2 (6mL) and MeCN (2mL). The reaction mixture was stirred for 2 days at room temperature. The work-up (A), column chromatography on silica gel, and crystallization afforded final products 1a - 3a and 1b - 3b.

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 140,p. 403 - 420

67
[ 54149-17-6 ]
(1S,3’R,6’R,7’S,8’E)-6-chloro-7'-((dimethyl(2-methyl-2-propanyl)silyl)oxy)-3,4-dihydro-2H,15’H-spiro[naphthalene-1,22’-[20]oxa[13]thia[1,12,14]triazatetracyclo[14.7.2.03,6.019,24]pentacosa[8,16,18,24]tetraen]-15'-one-13',13'-dioxide [ No CAS ]
(1S,3’R,6’R,7’S,8’E)-6-chloro-7'-((dimethyl(2-methyl-2-propanyl)silyl)oxy)-12'-(2-(2-methoxyethoxy)ethyl)-3,4-dihydro-2H,15’H-spiro[naphthalene-1,22'-[20]oxa[13]thia[1,12,14]triazatetracyclo[14.7.2.03,6.019,24]pentacosa[8,16,18,24]tetraen]-15'-one-13',13'-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		To a solution of (iS,3R,6R,7S,8E)-6-chioro-7?((dimethyi(2-methyi-2 propanvi)siiyI)oxy)-3,4.-dihydro2H. I 5H.-spiro[naphthalene- I ,2212(Hoxa[l 3jthiaj 1,1 2,l4itriazatetracyclo[14.7.2.0360?9?24lpentacosal 8,16,1 8,24Itet raen]-15- one 13,13?-dioxide (30 mg, 0.044 mmoi, Example 20. Step 1) in THF (0.5 mL) wad added 1.0 M soiuiion of lithium bis( rimethvisilvi)amide in THF (219 iL, 0.219 mmoi) and the mixture was stirred at room temperature for 30 mm, then 1-bromo-2-(2-methoxvethoxv)ethane (327 iL, 2185 mmol. Sigma15 Aldrich Co. St. Louis, MO) was added. The mixture thus obtained was heated at140 C for 3 h under microwave irradiation. The reaction mixture wasconcentrated under reduced pressure and the residue was purified by flash columnchromatography on silica gel (12 g HP silica, Teledyne Isco) eluting with 0% to25% ethyl acetate in hexanes to provide (iS,3R,6R,7?S,8E)-6-Chioro-7?-((dimethyi(2-methyi-2-propanyi)silyi)oxy)- 12-(2-(2-methoxyethoxy)ethyi)-3,4-diiiy dro-21-I, I 5H-spiro[naphthal ene- I ,22-[20]oxa[ I 3thia[i ,12, 14]triazatetracycio[14. 7.2.03?6.0?924jpentacosa[8, 16,1 S,24jtetraen-i5- one 13,13?-dioxide as a white solid (21 mg, 61% yield).

Reference： [1]Patent: WO2017/147410,2017,A1 .Location in patent: Page/Page column 215; 216

68
[ 54149-17-6 ]
[ 577967-89-6 ]
2-chloro-6-(2-(2-methoxyethoxy)ethoxy)quinoline [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 124 - 127

69
[ 54149-17-6 ]
3-((2,7-dibromo-9H-carbazole-9-yl)methyl)phenol [ No CAS ]
2,7-dibromo-9-(3-(2-(2-methoxyethoxy)ethoxy)benzyl)-9H-carbazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate; In 1,2-dimethoxyethane; for 60h;Reflux;	The 3-((2,7-dibromo-9H-carbazole-9-yl)methyl)phenol (400 mg, 0.928 mmol) prepared in Step (2) of Example 30 was dissolved in dimethoxyethane (10 mL), and then potassium carbonate (256 mg, 1.856 mmol) and <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (0.25 mL, 1.856 mmol) were added thereto, and the resulting mixture was refluxed under heating for two and half days. When the reaction was completed, the temperature was cooled to room temperature, and then the filtrate was concentrated under reduced pressure by filtering the reaction mixture. The concentrated solution was separated and purified with column chromatography (hexane/EtOAc, 10/1, v/v) to obtain a target compound (450 mg, 91.0%). (0508) 1H NMR (400 MHz, CDCl3) 6 7.87 (d, J=8.2 Hz, 2H), 7.47 (d, J=1.5 Hz, 2H), 7.37 (dd, J=8.3, 1.6 Hz, 2H), 7.21 (t, J=7.9 Hz, 1H), 6.81 (dd, J=8.1, 2.2 Hz, 1H), 6.69 (d, J=7.6 Hz, 1 H), 6.64 (d, J=1.9 Hz, 1H), 5.29 (s, 2H), 4.05 (t, J=4.9 Hz, 2H), 3.82-3.79 (m, 2H), 3.70-3.68 (m, 2H), 3.58-3.56 (m, 2H), 3.40 (s, 3H); 13C NMR (100 MHz, CDCl3) 6 159.34, 141.55, 137.64, 130.09, 123.06, 121.52, 121.43, 119.96, 118.67, 113.31, 113.06, 112.20, 71.94, 70.73, 69.64, 67.32, 59.09, 46.56.

Reference： [1]Patent: US2018/57527,2018,A1 .Location in patent: Paragraph 0507; 0508

70
[ 54149-17-6 ]
[ 2628-17-3 ]
1-[2-(2-methoxyethoxy)ethoxy]-4-vinylbenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%		0.058 mmol of the hydroxystyrene was put in a 500 ml round-bottom flask and dissolved by adding 50 ml of acetonitrile, and 0.071 mol of potassium t-butoxide was added dropwise thereto and then refluxed for 1 hour. Thereafter, 0.076 ml of <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> was slowly added dropwise thereto and then refluxed for 6 hours in a nitrogen atmosphere to perform a reaction. After the completion of the reaction, neutralization was performed using a hydrochloric acid aqueous solution, an organic layer was then extracted with an ethyl acetate/saturated base solution, and the organic layer was dried and filtered with anhydrous magnesium sulfate to remove remaining moisture. Thereafter, the solvent was removed under reduced pressure to obtain 10 g (96%) of a light brown liquid title compound of the following Formula (ii). 1H nuclear magnetic resonance spectroscopic data of the purified 1-(2-(2-methoxyethoxy)ethoxy)-4-vinylbenzene of Formula (ii) are as follows. 1H-NMR (500 MHz, CDCl3) delta 7.33-7.32 (d, J=8.5, Ar-H, 2H), delta 6.88-6.86 (d, J=8.5, Ar-H, 2H), delta 6.68-6.62 (q, J=9.5, 1H), delta 5.62-5.58 (d, J=17.5, 1H), delta 5.13-5.10 (d, J=11, 1H), delta 4.15-4.13 (t, J=5, 2H), delta 3.87-3.85 (t, J=5, 2H), delta 3.73-3.71 (t, J=4.7, 2H), delta 3.59-3.57 (t, J=4.5, 2H), delta 3.39 (s, 3H).

Reference： [1]Patent: US2018/72851,2018,A1 .Location in patent: Paragraph 0135; 0136

71
[ 54149-17-6 ]
[ 695-84-1 ]
1-[2-(2-methoxyethoxy)ethoxy]-4-vinylbenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%		0.058 mmol of hydroxystyrene was put into a 500 ml round-bottom flask, 50 ml of acetonitrile was added thereto to dissolve the hydroxystyrene, and then 0.07 1 mol ofpotassium t-butoxide was added dropwise to the flask, and the resulting solution was refluxed for 1 hout Subsequently, 0.076 mol of 1 -bromo-2-(2-methoxyethoxy)ethane was slowly added dropwise to the resultant and then refluxed in a nitrogen atmosphere for 6 hours to allow a reaction to occur therebetween. Afier the reaction was completed, the reaction product was neutralized with an aqueous hydrochloric acid solution, and then an organic layer was extracted with ethyl acetate/a saturated aqueous solution of a base, and the organic layer was dried with anhydrous magnesium sulfate and filtered to remove any remaining moisture. Thereafter, the solvent was removed under reduced pressure and, as a result, 10 g (96%) of a title compound represented by Formula (ii) below was obtained as a pale brown liquid. ?H NMR spectroscopic data of the purified 1 -(2-(2-methoxyethoxy)ethoxy)-4-vinylbenzene (ii) is as follows:

Reference： [1]Patent: US2018/244819,2018,A1 .Location in patent: Paragraph 0035; 0036

72
[ 54149-17-6 ]
[ 1357158-26-9 ]
C₂₀H₂₆O₄S₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%		Compound 1 (2.2 g, 8.7 mmol) was dissolved in DMSO (50 ml), potassium carbonate (3.6 g, 26.1 mmol) was added, and the mixture was stirred at room temperature for 30 minutes.Next, 2- (2-methoxyethoxy) ethyl bromide (manufactured by Tokyo Chemical Industry Co., Ltd.: 4.8 g, 26.1 mmol) was added and the mixture was stirred at room temperature for 12 hours.After the reaction solution was extracted with diisopropyl ether (250 ml), the organic solvent was washed with water.After distilling off the solvent, it was isolated and purified by silica gel column chromatography using hexane and ethyl acetate to obtain Compound 3 (2.4 g, yield 56%)

Reference： [1]Patent: JP2015/17052,2015,A .Location in patent: Paragraph 0091; 0092

73
[ 84661-56-3 ]
[ 54149-17-6 ]
1,1'-methylenebis(3-(2-(2-methoxyethoxy)ethyl)-1H-imidazol-3-ium)dibromide [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2019,vol. 2019,p. 1940 - 1943

74
[ 54149-17-6 ]
[ 615-21-4 ]
C₁₂H₁₇N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%		Under a nitrogen atmosphere, 2.00 g of the compound represented by the formula (C-7-1) and 20 mL of N,N-dimethylformamide were placed in a reaction vessel.While ice-cooling, 1.49 g of tertiary potassium butoxide was added, and the mixture was stirred at room temperature for 1 hour.While cooling with ice, a solution obtained by dissolving 2.44 g of the compound represented by the formula (C-7-2) in 3 mL of N,N-dimethylformamide was added dropwise.After stirring at room temperature for 5 hours, it was diluted with 100 mL of dichloromethane and poured into water.The organic layer was washed with brine and dried over sodium sulfate, and the solvent was evaporated.By subjecting column chromatography (alumina, dichloromethane) and recrystallization (dichloromethane/hexane), 3.04 g of the compound of formula (C-7) was obtained.The yield of the compound represented by the formula (C-7-1) was 94%.The reaction solution after the reaction showed a light coloration.
6.5 g		A reaction vessel was charged with 1.2 g of sodium amide and 5 mE of tetrahydrofuran in a nitrogen atmosphere. While the reaction vessel was cooled with ice, a solution mixture prepared by suspending 5.0 g of a compound represented by formula (11-6-1) in 10 mE of tetrahydrofuran was added dropwise, and the mixture was stirred at room temperature for 3 hours. Afier nitrogen gas was blown for two hours, a solution prepared by dissolving 6.1 g of a compound represented by formula (11-6-2) in 6 mE of tetrahydroffiran was added dropwise, and the mixture was stirred at room temperature for 5 hours. The resulting mixture was diluted with dichloromethane and washed with water and then brine. The product was purified by column chromatography (alumina, dichloromethane) and dispersion washing (hexane) to thereby obtain 6.5 g of a compound represented by formula (11-6-3).
6.5 g		1.2 g of sodium azide and 5 mL of tetrahydrofuran were placed in a reaction vessel under a nitrogen atmosphere.While cooling the mixture, 5.0 g of the compound represented by the formula (II-6-1) was suspended in 10 mL of tetrahydrofuran, and the mixture was stirred at room temperature for 3 hours. After blowing nitrogen gas for 2 hours, a solution obtained by dissolving 6.1 g of the compound represented by the formula (II-6-2) in 6 mL of tetrahydrofuran was added dropwise, and the mixture was stirred at room temperature for 5 hours. Dilute with dichloromethane and wash with water and saline. Purification by column chromatography (alumina, dichloromethane) and dispersion washing (hexane) afforded 6.5 g of the compound of formula (II-6-3).

Reference： [1]Patent: TW2019/14995,2019,A .Location in patent: Paragraph 0120; 0121
[2]Patent: US2020/165215,2020,A1 .Location in patent: Paragraph 0107-0108
[3]Patent: US2019/62256,2019,A1 .Location in patent: Paragraph 0212; 0213
[4]Patent: TW2019/12621,2019,A .Location in patent: Paragraph 0252; 0253

75
[ 54149-17-6 ]
C₁₈H₁₀N₄O₆S [ No CAS ]
4,7-bis(4-(2-(2-methoxyethoxy)ethoxy)phenyl)-5,6-dinitrobenzo[c][1,2,5]thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%		Compound AI-1 was synthesized by reference method (Anal. Chem. 2018, 90, 7953-7962.).Compound AI-1 (100 mg, 0.236 mmol) and potassium carbonate (130 mg, 0.944 mmol)It was added to 4 mL of DMF and stirred at 30 C for 1 h.Additional <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (173 mg, 0.944 mmol) was added for 4 h.After TLC detection, the reaction was completed, and water and ethyl acetate were added for extraction.The mixture was washed with saturated brine and dried over anhydrous sodium sulfate. Filter by suction and concentrate the filtrate under reduced pressure.The crude product was separated by column chromatography (dichloromethane:methanol = 30:1 v/v).Obtained a yellow solid 102mg,The yield was 70%.

Reference： [1]Patent: CN109369569,2019,A .Location in patent: Paragraph 0073-0076
[2]Analytical Chemistry,2019,vol. 91,p. 15577 - 15584

76
[ 28020-73-7 ]
[ 54149-17-6 ]
2,6-bis(1-(2-(2-methoxyethoxy)ethyl))-2,6-bis(benzimidazolyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43.2%	With sodium hydroxide; In acetonitrile; at 80℃;	According to the literature [39], we followed the N-alkylation reaction to carry out the synthesis of compound 3. A 100mL round bottom flask was charged with intermediate 2 (1mmol), <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (2.2mmol) and sodium hydroxide (4mmol) in acetonitrile (15mL). The reaction mixture was stirred at 80C overnight. After removing the solvent, the residue was dissolved in dichloromethane. The organic solution was washed with water three times and then dried over anhydrous magnesium sulfate. Purified by column chromatography on silica gel with gradient eluents of petroleum ether and ethyl acetate, the pure target compound 3 was afforded.

Reference： [1]Dyes and Pigments,2019,vol. 167,p. 164 - 173

77
[ 29914-81-6 ]
[ 54149-17-6 ]
1,3-bis(1-(2-(2-methoxyethoxy)ethyl)-1H-benzimidazol-2-yl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47.5%	With sodium hydroxide; In acetonitrile; at 80℃;	According to the literature [39], we followed the N-alkylation reaction to carry out the synthesis of compound 3. A 100mL round bottom flask was charged with intermediate 2 (1mmol), <strong>[54149-17-6]1-bromo-2-(2-methoxyethoxy)ethane</strong> (2.2mmol) and sodium hydroxide (4mmol) in acetonitrile (15mL). The reaction mixture was stirred at 80C overnight. After removing the solvent, the residue was dissolved in dichloromethane. The organic solution was washed with water three times and then dried over anhydrous magnesium sulfate. Purified by column chromatography on silica gel with gradient eluents of petroleum ether and ethyl acetate, the pure target compound 3 was afforded.

Reference： [1]Dyes and Pigments,2019,vol. 167,p. 164 - 173

78
[ 54149-17-6 ]
[ 64318-28-1 ]
tert-butyl 4-(2-(2-methoxyethoxy)ethoxy)phenethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 60℃; for 22h;Inert atmosphere;	l-Bromo-2-(2-methoxyethoxy)ethane (1.83 g, 10 mmol, diluted in 10 mL of dried DMF) was added dropwise to a stirred mixture of tert- butyl 4-hydroxyphenethylcarbamate (2.61 g, 11 mmol) and NaH (0.44 g, 11 mmol, 60% dispersion in mineral oil) in dry DMF (40 mL) under N2 at 0 C. The reaction was stirred at room temperature for 14 h. After this time, the reaction mixture was stirred at 60 C for 8 h. The reaction was quenched with ice-water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography to afford the title compound as colorless oil (2.311 g, 68% yield). NMR (500 MHz, CDCb) S: 7.19- 7.01 (m, 2H), 6.93-6.81 (m, 2H), 4.58 (s, 1H), 4.13 (dd, J= 9.8, 4.9 Hz, 2H), 3.86 (dd, J= 9.5, 5.1 Hz, 2H), 3.79-3.67 (m, 2H), 3.65-3.53 (m, 2H), 3.40 (dd, J= 4.0, 1.8 Hz, 3H), 3.34 (s, 2H), 2.73 (s, 2H), 1.44 (s, 9H).

Reference： [1]Patent: WO2020/2969,2020,A1 .Location in patent: Page/Page column 37

79
[ 54149-17-6 ]
[ 64318-28-1 ]
2-(4-(2-(2-methoxyethoxy)ethoxy)phenyl)ethanamine [ No CAS ]

Reference： [1]Patent: WO2020/2969,2020,A1

80
[ 54149-17-6 ]
[ 94838-59-2 ]
tert-butyl 4-((2-(2-methoxyethoxy)ethyl)amino)phenethylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With caesium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 110℃; for 2h;	A stirred mixture of l-bromo-2-(2-methoxyethoxy)ethane (0.366 g, 2 mmol), fert-butyl 4- aminophenethylcarbamate (0.614 g, 2.6 mmol), cesium carbonate (0.847 g, 2.6 mmol) and Nal (0.03 g, 0.2 mmol) in DMF (15 mL) was heated at 110 C for 2 h. The reaction mixture was diluted with water (40 mL) and extracted with ethyl acetate (2x60 mL). The organic layer was washed with water (30 mL) and brine (30 mL), concentrated in vacuo, and purified by column chromatography to afford the title compound as light-yellow oil (0.17 g, 25% yield). NMR (500 MHz, DMSO-riri) S: 6.88 (d, J= 8.3 Hz, 2H), 6.80 (d, J= 6.1 Hz, 1H), 6.50 (t, J= 7.0 Hz, 2H), 5.34 (t, J= 5.5 Hz, 1H), 3.53 (t, J= 5.0 Hz, 4H), 3.45 (dd, J= 5.7, 3.7 Hz, 2H), 3.24 (s, 3H), 3.14 (q, J= 5.7 Hz, 2H), 3.03 (dd, J= 14.3, 6.1 Hz, 3H), 2.52 (s, 2H), 1.37 (s, 9H).

Reference： [1]Patent: WO2020/2969,2020,A1 .Location in patent: Page/Page column 78

81
[ 54149-17-6 ]
α,α′-dihydroxytetrastyrene [ No CAS ]
C₃₆H₄₀O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium carbonate; In acetone; at 60℃; for 12h;Inert atmosphere;	Place alpha, alpha?-dihydroxytetrastyrene (0.364 g, 1 mmol) and potassium carbonate (1.38 g, 10 mmol) in a 150 mL round bottom bottle; add 50 mL of dry acetone under nitrogen and stir until dissolved; add 1 -Bromo-2- (2-methoxyethoxy) ethane (0.732g, 4mmol); warm to 60 C, react for 12h; extract with ethyl acetate (3 × 50mL), combine organic phases; use anhydrous After drying with magnesium sulfate, the solvent was removed; n-hexane / ethyl acetate (75/25) was used as the mobile phase for column chromatography to obtain a pale yellow viscous liquid with a yield of 88%.

Reference： [1]Patent: CN111039764,2020,A .Location in patent: Paragraph 0040; 0044-0046

82
[ 61822-18-2 ]
[ 54149-17-6 ]
C₁₉H₂₃NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 2,7-Dimethoxy-9H-Carbazole With sodium hydride In tetrahydrofuran; kerosene at 50℃; for 0.5h; Stage #2: 2-bromoethyl 2-methoxyethyl ether In tetrahydrofuran; kerosene at 20℃; for 3h;	1 Synthesis of compound A (compound 1 intermediate): Take 2,7-dimethoxycarbazole powder and 60% sodium hydride kerosene mixture, stir in anhydrous tetrahydrofuran at 50°C for 0.5h, then add 1-bromo-2-(2-methoxyethoxy)ethane was reacted at room temperature for 3 h to obtain compound A. It was a brown oily liquid with a yield of 87%.

Reference： [1]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN113943300, 2022, A Location in patent: Paragraph 0058-0062

83
[ 1009564-95-7 ]
[ 54149-17-6 ]
[ 2838094-63-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	In N,N-dimethyl-formamide at 120℃; for 48h;

Reference： [1]Wang, Li-Juan; Bai, Sha; Han, Ying-Feng [Journal of the American Chemical Society, 2022, vol. 144, # 35, p. 16191 - 16198]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	54149-17-6	MDL No. :	MFCD00000238
Formula :	C₅H₁₁BrO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HUXJXNSHCKHFIL-UHFFFAOYSA-N
M.W :	183.04	Pubchem ID :	123532
Synonyms :		Chemical Name :	1-Bromo-2-(2-methoxyethoxy)ethane

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	5
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	36.19
TPSA :	18.46 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.03 cm/s

Log Po/w (iLOGP) :	2.28
Log Po/w (XLOGP3) :	0.55
Log Po/w (WLOGP) :	1.04
Log Po/w (MLOGP) :	0.78
Log Po/w (SILICOS-IT) :	1.34
Consensus Log Po/w :	1.2

[ CAS No. 54149-17-6 ] {[proInfo.proName]}

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[ 54149-17-6 ] Synthesis Path-Downstream 1~83

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[ 54149-17-6 ]

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-0.99
Solubility :	18.7 mg/ml ; 0.102 mol/l
Class :	Very soluble
Log S (Ali) :	-0.51
Solubility :	56.6 mg/ml ; 0.309 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.22
Solubility :	1.11 mg/ml ; 0.00604 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.61

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P305+P351+P338	UN#:	N/A
Hazard Statements:	H227-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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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.
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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:
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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
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P401
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[ CAS No. 54149-17-6 ] {[proInfo.proName]}

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[ 54149-17-6 ]