Name: 103-16-2|4-Benzyloxyphenol|98%
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SKU: A182754
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1
[ 100-39-0 ]
[ 123-31-9 ]
[ 103-16-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate; In acetone;Reflux; Inert atmosphere;	To a solution of hydroquinone (12.1 g, 110 mmol) in 100 mL acetone was added K2CO3 (7.6 g, 55 mmol) and benzyl bromide (9.4 g, 55 mmol) at room temperature, the resulting mixture was heated under reflux overnight. After cooling to room temperature, the reaction mixture was filtered and the filtrate was concentrated. The residue was taken up in EtOAc (300 mL) and washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was subjected to flash column chromatography on silica gel (EtOAc-petroleum ether, 10:90) provided monobenzylhydroquinone 11 (8.0 g,73 % yield) as a white colored solid.1H NMR (400 MHz, acetone-d6) delta 7.98 (brs, 1H), 7.46-7.29 (m, 5H), 6.87 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 5.01 (s, 2H); 13C NMR (100 MHz, acetone-d6) delta 153.0, 152.3, 138.8, 129.1, 128.4, 128.3, 116.6, 116.6, 71.0; HRESIMS calcd for C13H11O2 [M-H]-: 199.0765, found 199.0758.
55%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 10h;Inert atmosphere;	Hydroquinone (2.4g, 22mmol) was dissolved in DMF (50mL), and then anhydrous potassium carbonate (3.7g, 26mmol) and benzyl bromide (1.5g, 8.8mmol) were added and reacted at room temperature for 10h.The reaction was stopped, water (100 mL) was added to the reaction solution, dilute hydrochloric acid was added to adjust the pH to 3, and ethyl acetate was extracted (80 mL × 3).The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (PE / EtOAc (v / v) = 15/1) to obtain 930 mg of light yellow oily liquid, yield: 55%.
25%	With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 4h;	4-Benzyloxy-phenol (JRL01016) To a stirred solution of hydroquinone (7.00 g, 63.4 mmol) in DMF (100 mL) at 0 C. under nitrogen was added NaH (60%, 2.54 g, 63.4 mmol). After stirring for 30 min, benzyl bromide (7.72 mL, 63.4 mmol) was added and the resulting mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with ethyl acetate (300 mL) and the organic layer separated was washed with brine (300 mL, 4*100 mL), dried (Na2SO4), filtered and evaporated to give the crude product which was fractionated by flash chromatography (hexane/EtOAc 3:1) to give JRL01016 as a white solid (3.11 g, 25%); Rf 0.35 (Hexane/EtOAc 3:1); 1H (400 MHz CDCl3) 4.61 (1H, s OH), 5.01 (2H, s, CH2), 6.74 (2H, AA'BB'), 6.85 (2H, AA'BB'), and 7.28-7.44 (5H, m).

Reference： [1]Tetrahedron Letters,2019,vol. 60
[2]RSC Advances,2019,vol. 9,p. 23295 - 23301
[3]Tetrahedron,2007,vol. 63,p. 10698 - 10708
[4]Patent: CN107344940,2020,B .Location in patent: Paragraph 0640-0645
[5]Patent: US2004/19016,2004,A1 .Location in patent: Page/Page column 65
[6]Journal of Materials Chemistry C,2020,vol. 8,p. 1083 - 1088
[7]Justus Liebigs Annalen der Chemie,1883,vol. 221,p. 369

2
[ 103-16-2 ]
[ 106-89-8 ]
[ 28150-30-3 ]

Yield	Reaction Conditions	Operation in experiment
68%	With caesium carbonate; In N,N-dimethyl-formamide; at 75℃; for 72h;	To a solution of 4-(benzyloxy)phenol (15.0 g, 74.9 mmol) and epichlorohydrin (30 mL, 384 mmol) in DMF (200 mL) was added Cs2CO3 (51.2 g, 157 mmol). The mixture was heated to 75 C. for 3 days. The reaction mixture was cooled to room temperature, and then partitioned in 1:1 ethyl acetate/H2O (600 mL). The organic layer was collected, washed with H2O (3×250 mL), dried (MgSO4), filtered, and concentrated under reduced pressure to give 38 g of a clear, dark brown liquid. The liquid was purified on SiO2 (300 g; 50-100% CH2Cl2/hexanes) to give the desired product as a white solid (13 g, 68% yield). TLC (SiO2, CH2Cl2): Rf=0.64. 1H NMR (400 MHz, CDCl3): 7.55-7.28 (m, 5H), 6.91 (d, J=9.3, 2H), 6.86 (d, J=9.3, 2H), 5.03 (s, 2H), 4.17 (dd, J=11.0, 3.2, 1H), 3.95-3.88 (m, 1H), 3.36-3.33 (m, 1H), 2.91 (t, J=4.8, 1H), 2.75 (dd, J=4.9, 2.6, 1H).
68%	With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 75℃; for 72h;	EXAMPLE 40; 1- {3- [4- (BENZOOXAZOL-2-YLOXY)-PHENOXY]-2-HYDROXY-PROPYL}-4-PHENYL-PIPERIDIN-4- ol; A. 2- (4-BENZVLOXV-PHENOXVMEFHY)-OXIRANE; To a solution of 4- (benzyloxy) phenol (15.0 g, 74.9 MMOL) and epichlorohydrin (30 mL, 384 MMOL) in DMF (200 mL) was added CS2CO3 (51.2 g, 157 mmol). The mixture was heated to 75 C for 3 days. The reaction mixture was cooled to room temperature, and then partitioned in 1: 1 ethyl ACETATE/H20 (600 mL). The organic layer was collected, washed with H20 (3 x 250 mL), dried (MGS04), filtered, and concentrated under reduced pressure to give 38 g of a clear, dark brown liquid. The liquid was purified on SI02 (300 g; 50-100% CH2CI2/HEXANES) to give the desired product as a white solid (13 g, 68% yield). TLC (SiO2, CH2Cl2): Rf-0.64. 1H NMR (400 MHz, CDCl3); 7.55-7.28 (m,5H), 6.91 (D,J=9.3,2H),6,86 (d,J=9.3,2H), 5,03 (S,2H), 4.17 (dd,J=11.0, 3.2, 1 H), 3.95-3. 88 (m, 1 H), 3.36-3. 33 (m, 1 H), 2.91 (t, J = 4.8, 1 H), 2.75 (dd, J = 4.9, 2.6, 1 H)
	With potassium carbonate;	EXAMPLE 1 Preparation of 1-(p-benzyloxyphenoxy)-2,3-epoxypropane 25 g of p-benzyloxyphenol, 165 ml of epichlorohydrin, and 34.5 g of potassium carbonate were refluxed while stirring for 4 hours. The mixture was cooled down to room temperature and filtered, whereupon it was evaporated to dryness. The product was recrystallized from the smallest possible amount of diisopropyl ether. M.p. 68 C.

With sodium hydroxide; In ice-water; water; dimethyl sulfoxide;

EXAMPLE 37 (R,S)-1-(4-Benzyloxyphenoxy)-2-hydroxy-3-isopropylaminopropane To a solution of 200 g (1 mol) p-benzyloxyphenol in 2.5 DMSO was added 375 ml 4 N NaOH followed by 216 ml of epichlorohydrin and the resulting mixture was stirred at room temp for 3 hr. The reaction was poured into 6 l of an ice-water mixture and extracted with CH2 Cl2 (3*1 l). The organic extracts were washed in turn with H2 O (3*500 ml), and then were combined, dried (Na2 SO4) and evaporated to dryness. The resulting crude solid was crystallized from ether to give (R,S)-1-(4-benzyloxyphenoxy)-2,3-epoxypropane in two crops.

Reference： [1]Bioorganic and medicinal chemistry,2003,vol. 11,p. 3513 - 3527
[2]Patent: US2008/194630,2008,A1 .Location in patent: Page/Page column 41
[3]Patent: WO2005/12296,2005,A1 .Location in patent: Page/Page column 110
[4]Patent: US2805170,1953,
[5]Patent: US4080471,1978,A
[6]Patent: US4202978,1980,A
[7]Tetrahedron Letters,2013,vol. 54,p. 6307 - 6309

3
[ 103-16-2 ]
[ 109-64-8 ]
[ 80199-92-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In dichloromethane; acetone;	EXAMPLE 15 Preparation of 1-benzyloxy-4-(3-bromopropoxy)benzene A mixture of 4-benzyloxyphenol (50 g), 1,3-dibromopropane (101 g) and powdered anhydrous potassium carbonate (17.3 g) in acetone (500 ml) was stirred under reflux for 30 hours. The solids were removed by filtration and the filtrate was evaporated to dryness in vacuo. The residue was dissolved in 300 ml of dichloromethane and the resulting solution was washed with 10% sodium hydroxide solution to remove unreacted p-benzyloxyphenol. The dichloromethane extract was dried over potassium carbonate, concentrated in vacuo and distilled giving 33.4 g of 1-benzyloxy-4-(3-bromopropoxy)benzene; bp 180-195 (0.6 mm) (41% yield, 98% pure by gas chromatography). The structure was confirmed by mass spectrum analysis.
88%	With potassium carbonate; In acetonitrile; for 66h;Heating / reflux;	To a stirring solution of 4-benzyloxyphenol (25 g, 124.9 mmol) in CH3CN (125 mL) was added dibromopropane (63 mL, 624 mmol) and K2CO3 (34.5 g, 250 mmol). This brown suspension was heated at reflux and allowed to stir for 66 h. The suspension was then cooled to room temperature and filtered twice through diatomaceous earth pads. The pads were rinsed with CH3CN, and the combined filtrates were concentrated under reduced pressure. The resultant oil was purified on SiO2 (300 g; 33% CH2Cl2/hexanes) to give 35.4 g (110 mmol, 88% yield) of a brown solid. 1H NMR (400 MHz, CDCl3): 7.46-7.29 (m, 5H), 6.85 (q, J=8.1, 2H), 6.82 (q, J=7.2, 2H), 5.03 (s, 2H), 4.06 (t, J=5.8, 2H), 3.61 (t, J=6.5, 2H), 2.39 (m, J=6.2, 2H).
88%	With potassium carbonate; In acetonitrile; for 66h;Heating / reflux;	EXAMPLE 2; 1- [3- (4-BENZYLOXY-PHENOXY)-PROPYL]-BROMIDE; To a stirring solution of 4-benzyloxyphenol (25 g, 124.9 MMOL) in CH3CN (125 mL) was added dibromopropane (63 mL, 624 MMOL) and K2CO3 (34.5 g, 250 MMOL). This brown suspension was heated at reflux and allowed to stir for 66 h. The suspension was then cooled to room temperature and filtered twice through diatomaceous earth pads. The pads were rinsed with CH3CN, and the combined filtrates were concentrated under reduced pressure. The resultant oil was purified on SI02 (300 g; 33% CH2CI2/HEXANES) to give 35.4 g (110 mmol, 88% yield) of a brown SOLID. 1H NMR (400 MHz, CDC13) : 7.46-7. 29 (m, 5H), 6.85 (Q, J = 8.1, 2H), 6. 82 (q, J= 7.2, 2H), 5.03 (s, 2H), 4.06 (t, J = 5.8, 2H), 3. 61 (t, J = 6.5, 2H), 2.39 (m, J = 6.2, 2H)

88%	With potassium carbonate; In acetonitrile; for 66h;Heating / reflux;	Example 2 1-[3-(4-Benzyloxy-phenoxy)-propyl]-bromide To a stirred solution of 4-benzyloxyphenol (25 g, 124.9 mmol) in CH3CN (125 mL) was added dibromopropane (63 mL, 624 mmol) and K2CO3 (34.5 g, 250 mmol). This brown suspension was heated at reflux and stirred for 66 h. The suspension was then cooled to rt and filtered twice through diatomaceous earth pads. The pads were rinsed with CH3CN, and the combined filtrates were concentrated. The resultant oil was purified on SiO2 (300 g; 33% CH2Cl2/hexanes). The desired fractions were combined and concentrated to give 35.4 g (110 mmol, 88%) of a brown solid. 1H NMR (400 MHz, CDCl3): 7.46-7.29 (m, 5H), 6.85 and 6.82 (q, J=8.0 and 7.2, 4H), 5.03 (s, 2H), 4.06 (t, J=5.8, 2H), 3.61 (t, J=6.5, 2H), 2.39 (m, J=6.2, 2H).
63%	With potassium carbonate; In acetone;	EXAMPLE 28 3-[(4-Phenylmethoxy)phenoxy]propyl bromide A mixture of 10 g (0.05 mol) of 4-benzyloxyphenol, 51 ml (0.5 mol) of 1,3-dibromopropane and 20.7 g (0.15 mol) of potassium carbonate in 150 ml of acetone was stirred at reflux for 24 hours. The solvent and excess 1,3-dibromopropane were removed at reduced pressure and the residue was crystallized from methanol to give 10 g (63% yield, mp 53-56) of 3-[(4-phenylmethoxy)phenoxy]propyl bromide.

Reference： [1]Patent: US4471116,1984,A
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4528 - 4532
[3]Patent: US2008/194630,2008,A1 .Location in patent: Page/Page column 28
[4]Patent: WO2005/12296,2005,A1 .Location in patent: Page/Page column 76-77
[5]Patent: US2006/223792,2006,A1 .Location in patent: Page/Page column 22
[6]Patent: US5374772,1994,A
[7]Journal of Medicinal Chemistry,1965,vol. 8,p. 356 - 367
[8]Journal of Medicinal Chemistry,2003,vol. 46,p. 4728 - 4740
[9]European Journal of Medicinal Chemistry,2009,vol. 44,p. 4218 - 4226

4
[ 51594-55-9 ]
[ 103-16-2 ]
[ 122797-04-0 ]

Yield	Reaction Conditions	Operation in experiment
73.4%	With cesium fluoride; In N,N-dimethyl-formamide; at 50℃; for 72h;	(S)-2-((4-(benzyloxy)phenoxy)methyl)oxirane (13a) A mixture of 4-(benzyloxy)phenol, 11 (50 g, 249.71 mmol) and (R)-2-(chloromethyl)oxirane, 12a (69.31 g, 749.14 mmol) in 500 mL of DMF (was added CsF (113.79 g, 749.14 mmol). The reaction mixture was stirred at 50 C. for 3 days. The resulting reaction mixture was then partitioned between water (1 L) and EtOAc (2 L). The organic layer was washed with 3 times with water (900 mL, each), and brine, and then dried over Na2SO4. The organic extract was concentrated under reduced pressure and purified by silica column (Pet ether:EtOAc, 4:1) to give (S)-2-((4-(benzyloxy)phenoxy)methyl)oxirane, 13a (47 g, 73.4%) as white solid. The 1H NMR was consistent with the structure.
73.4%	With cesium fluoride; In N,N-dimethyl-formamide; at 50℃; for 72h;	CsF (113.79 g, 749.14 mmol) was added with stirring to a mixture of 4-(benzyloxy)phenol,(50 g, 249.71 mmol) and (R)-2-(chloromethyl)oxirane, (R)-5 (69.31 g, 749.14 mmol) in DMF(500mL). The reaction mixture was stirred at 50C for 3 days. The reaction mixture was thenpartitioned between water (1 L) and EtOAc (2 L). The organic layer was washed with water(3x900 mL), brine, and then dried over Na2SO4. The filtered organic extract was concentratedunder reduced pressure and purified by silica column (pet ether:EtOAc, 4:1) to give (S)-2-((4-(benzyloxy)phenoxy)methyl)oxirane, (S)-6 (47 g, 73.4%) as a white solid.

Reference： [1]Chemistry Letters,1991,p. 1109 - 1112
[2]Patent: US2016/184315,2016,A1 .Location in patent: Paragraph 0133; 0136
[3]PLoS ONE,2017,vol. 12

5
[ 28598-81-4 ]
[ 103-16-2 ]
9-(4-Benzyloxy-phenoxy)-nonanoic acid ethyl ester [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals (1969-1991),1985,vol. 123,p. 247 - 256

6
[ 55099-31-5 ]
[ 103-16-2 ]
10-(4-Benzyloxy-phenoxy)-decanoic acid ethyl ester [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals (1969-1991),1985,vol. 123,p. 247 - 256

7
[ 103-16-2 ]
[ 4025-71-2 ]
2-Phenyl-ethanesulfonic acid 4-benzyloxy-phenyl ester [ No CAS ]

Reference： [1]Journal of general chemistry of the USSR,1985,vol. 55,p. 2354 - 2358
Zhurnal Obshchei Khimii,1985,vol. 55,p. 2649 - 2654

8
[ 103-16-2 ]
[ 50909-50-7 ]
[ 124501-19-5 ]

Yield	Reaction Conditions	Operation in experiment
67.4%	With triethylamine; In butanone; at 0℃; for 4.5h;Cooling with ice;	In an experiment,4-benzyloxy phenol (5 g, 0.025 mol) was placed in a 500 ml two-necked roundbottomflask with ethyl methyl ketone as solvent, which was kept in an ice bath. Triethylamine(3 ml, 0.03mol) was added to the reaction solution on stirring. To this, 4-dodecyloxybenzoyl chloride-which was prepared from acid by reacting with thionyl chloride-wasslowly added through a pressure equalizing dropping funnel for 30 minutes while maintainingthe temperature at 0C. The stirring was continued for 4 hours and then the precipitatedtriethylamine salt was filtered and the solvent was removed from the solution under reduced pressure. The solid obtained was washed with 4% potassium hydroxide solution twice toremove unreacted acid, phenol, further washed with water, then dried and recrystallized.Yield: 67.4%, m.p. 78C, FT-IR (KBr, cm-1): 2921, 2852 (C Hstr), 1728 (C Ostr),1683, 1606, 1511 (C Cstr aromatic), 1464, 1333 (C Hben), 1251, 1200, 1170 (C OCasym & sym str of ester and ether); 1H-NMR ppm (CDCl3): 8.13 (d, 2H), 7.46 (d, 2H), 7.40(t, 2H), 7.35 (t, 1H), 7.12 (d, 2H), 7.02 (d, 2H), 6.98 (d, 2H), 5.07 (s, 2H), 4.04 (t, 2H),1.84 (m, 2H), 1.48 (m, 2H), 1.37 (m, 16H), 0.90 (t, 3H); 13C-NMR ppm (CDCl3): 165.42,163.57, 156.50, 144.83, 136.98, 132.34, 128.72, 128.13, 127.61, 122.70, 121.69, 115.56,114.35, 70.51, 68.40, 32.05, 29.79, 29.77, 29.76, 29.73, 29.70, 29.50, 29.22, 26.10, 22.83,and 14.27.
	In pyridine;	REFERENTIAL EXAMPLE 15 Synthesis of 4'-hydroxyphenyl 4-dodecyloxybenzoate STR52 In 30 ml of pyridine, 3.25 g of 4-dodecyloxybenzoic acid chloride was reacted with 2.0 g of hydroquinone monobenzyl ether to obtain 4.4 g of 4'-benzyloxyphenyl 4-dodecyloxybenzoate.

Reference： [1]Molecular Crystals and Liquid Crystals,2013,vol. 582,p. 1 - 14
[2]Helvetica Chimica Acta,1993,vol. 76,p. 865 - 876
[3]Molecular Crystals and Liquid Crystals (1969-1991),1987,vol. 151,p. 147 - 154
[4]Patent: US5045228,1991,A

9
[ 103-16-2 ]
[ 79352-66-2 ]

Yield	Reaction Conditions	Operation in experiment
97.6%	With bromine; calcium carbonate; In methanol; dichloromethane; at 20℃; for 0.5h;	Intermediate 16; 2-[4-(2-Bromo-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid methyl ester; Step A; 4-Benzyloxy-phenol (32.04 g, 160.2 mmol) is dissolved in 550 mL of dichloromethane and 20 mL methanol. Powdered calcium carbonate (21.83 g, 218.1 mmol, 1.36 equiv.) is suspended in the solution. While the suspension is vigorously stirred, a solution of bromine (8.30 mL, 161.5 mmol, 1.01 equiv.) in 50 mL dichloromethane is added dropwise. After the addition is completed, the suspension is stirred at room temperature for 30 min, then the solids are filtered off. The filtrate is dried over solid NaHCO3 and MgSO4, then filtered and concentrated to yield an oil. Precipitation of unreacted 4-benzyloxy-phenol using diethyl ether/petroleum ether at -200C yielded 4-benzyloxy-2-bromo-phenol 10 as a colorless oil that slowly solidified (43.65 g, 156.4 mmol, 97.6%). 1H-NMR (400 MHz, CDCl3) delta = 7.38 (m, 5H), 7.10 (d, J= 2.8 Hz, IH), 6.94 (d, J= 8.9 Hz, IH), 6.87 (dd, J= 8.9, 2.8 Hz, IH), 4.99 (s, 2H).
72%	With bromine; In chloroform; at 0 - 20℃; for 1h;	Intermediate 4-(benzyloxy)-2-bromophenol [79352-66-2] 10 was prepared following the procedure of Dodsworth.[1] In a cooling mixture (0 C) of 4-(benzyloxy)phenol [103-16-2] 9 (10.00 g, 49.94 mmol, 1.00 equiv) in CHCl3 (200 ml) was added dropwise bromine (8.06 g, 50.44 mmol, 1.01 equiv). After the end of the addition, the reaction mixture was stirred for 1 hour at room temperature. After extractive workup, the crude product was purified by flash column chromatography (DCM/Petroleum ether 1:1) followed by a recrystallization with hexane to yield 10 (10.03 g, 72%) as a white solid. The spectroscopic data were identical to those described in the literature
	With bromine; calcium carbonate; In methanol; dichloromethane; at 20℃; for 0.5h;	Intermediate 76; 2- (4-Hydroxy-2-methyl-phenoxy) -2-methyl- propionic acid methyl ester; Step A; 4-Benzyloxy-phenol (32.04 g, 160 mmol) is dissolved in of DCM (550 tnL) and methanol (20 mL) . Powdered calcium carbonate (21.83 g, 218 mmol) is suspended into the solution. While stirring vigorously, a solution of bromine (8.30 mL, 162 mmol) in DCM (50 mL) is added dropwise. After the addition is completed, the suspension is stirred at rt for 30 min, then the solids are' filtered off. The filtrate is dried over solid NaHCO3 and MgSO4, then filtered and concentrated to yield an oil. Recrystallization from diethyl ether/petroleum ether at -200C yielded 4-benzyloxy-2-bromo-phenol 71 as a colourless oil that slowly solidified: 1H-NMR (400 MHz, CDCl3) delta = 7.38 (m, 5H), 7.10 (d, J = 2.8 Hz, IH), 6.94 (d, J = 8.9 Hz, IH) , 6.87 (dd, J" = 8.9, 2.8 Hz, IH) , 4.99 (s, 2H) .

		EXAMPLE 30A 4-Benzyloxy-2-bromophenol 183 g of 4-benzyloxyphenol (914 mmol) are brominated according to the literature (J. C. S Perkin 1, 1981, 223). Following recrystallization from petroleum ether (with 5% ether), the product is obtained as a colorless solid. Yield: 189 g (74.1% of theory) MS (DCl, NH3): m/z (%)=296/298 (M+18) (100) 1H-NMR (200 MHz, CDCl3): delta=4.96 (s, 2H); 5.19 (s, 1H); 6.70-6.95 (m, 2H); 7.10 (d, 1H); 7.39-7.45 (m, 5H).
	With bromine; calcium carbonate; In methanol; dichloromethane; at 20℃; for 0.5h;	Intermediate 66; 2-(4-Hydroxy-2-methyl-phenoxy)-2-methyl-propionic acid methyl ester; Step A; 4-Benzyloxy-phenol (32.04 g, 160 mmol) is dissolved in of DCM (550 mL) and methanol (20 mL). Powdered calcium carbonate (21.83 g, 218 mmol) is suspended into the solution. While stirring vigorously, a solution of bromine (8.30 mL, 162 mmol) in DCM (50 mL) is added dropwise. After the addition is completed, the suspension is stirred at rt for 30 min, then the solids are filtered off. The filtrate is dried over solid NaHCO3 and MgSO4, <n="46"/>then filtered and concentrated to yield an oil. Recrystallization from diethyl ether/petroleum ether at -20C yielded 4-benzyloxy-2-bromo-phenol 61 as a colourless oil that slowly solidified: 1H-NMR (400 MHz, CDCl3) delta = 7.38 (m, 5H), 7.10 (d, J= 2.8 Hz, IH), 6.94 (d, J= 8.9 Hz, IH)3 6.87 (dd, J= 8.9, 2.8 Hz, IH), 4.99 (s, 2H).

Reference： [1]Patent: WO2007/56496,2007,A1 .Location in patent: Page/Page column 25
[2]Journal of the Chemical Society. Perkin transactions I,1981,p. 2120 - 2124
[3]Chemistry - A European Journal,2000,vol. 6,p. 2874 - 2894
[4]Tetrahedron Letters,2012,vol. 53,p. 2432 - 2435
[5]Patent: WO2007/56366,2007,A2 .Location in patent: Page/Page column 57
[6]Patent: US2004/97498,2004,A1
[7]Patent: WO2007/56497,2007,A1 .Location in patent: Page/Page column 44-45

10
[ 50666-95-0 ]
[ 103-16-2 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 773 - 776
[2]Catalysis science and technology,2013,vol. 3,p. 2541 - 2545
[3]Synthetic Communications,2000,vol. 30,p. 3565 - 3568
[4]Tetrahedron Letters,1992,vol. 33,p. 5129 - 5132
[5]Chemical and Pharmaceutical Bulletin,2003,vol. 51,p. 1220 - 1221
[6]Tetrahedron,2004,vol. 60,p. 7973 - 7981
[7]Tetrahedron Letters,1999,vol. 40,p. 7293 - 7294
[8]Tetrahedron Letters,1997,vol. 38,p. 4721 - 4724
[9]Organic Letters,2000,vol. 2,p. 489 - 491
[10]Chemistry Letters,1999,p. 1223 - 1224
[11]Synthetic Communications,2002,vol. 32,p. 133 - 137
[12]Journal of the American Chemical Society,2004,vol. 126,p. 8755 - 8759
[13]Journal of Organic Chemistry,1999,vol. 64,p. 4211 - 4213

11
[ 103-16-2 ]
[ 33863-86-4 ]
[ 148731-03-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane for 2h; Heating; Yield given;
	With triethylamine In butanone at 0℃; for 4.5h; Cooling with ice;	General procedure: In an experiment,4-benzyloxy phenol (5 g, 0.025 mol) was placed in a 500 ml two-necked roundbottomflask with ethyl methyl ketone as solvent, which was kept in an ice bath. Triethylamine(3 ml, 0.03mol) was added to the reaction solution on stirring. To this, 4-dodecyloxybenzoyl chloride-which was prepared from acid by reacting with thionyl chloride-wasslowly added through a pressure equalizing dropping funnel for 30 minutes while maintainingthe temperature at 0C. The stirring was continued for 4 hours and then the precipitatedtriethylamine salt was filtered and the solvent was removed from the solution under reduced pressure. The solid obtained was washed with 4% potassium hydroxide solution twice toremove unreacted acid, phenol, further washed with water, then dried and recrystallized.

Reference： [1]Deschenaux, Robert; Marendaz, Jean-Luc; Santiago, Julio [Helvetica Chimica Acta, 1993, vol. 76, # 2, p. 865 - 876]
[2]Reddy, M. Kesava; Reddy, K. Subramanyam; Prakash; Narasimhaswamy [Molecular Crystals and Liquid Crystals, 2013, vol. 582, # 1, p. 1 - 14]

12
[ 31255-26-2 ]
[ 103-16-2 ]
[ 113816-32-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium hydroxide In ethanol for 5h; Heating;

Reference： [1]Bauer, Martin; Mueller, Walter Manfred; Mueller, Ute; Rissanen, Kari; Voegtle, Fritz [Liebigs Annalen, 1995, # 4, p. 649 - 656]

13
[ 5414-19-7 ]
[ 103-16-2 ]
1-(benzyloxy)-4-[2-(2-bromoethoxy)ethoxy]benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium hydroxide; In tetrahydrofuran; water; at 70℃;	Into a 1000-mL round -bottom flask was placed a solution of 4-(benzyloxy)phenol (5 g, 24.97 mmol, 1.00 equiv) in tetrahydrofuran (200 mL), 37 %NaOH (200 mL), and l-bromo-2- (2-bromoethoxy)ethane (57.5 g, 247.94 mmol, 10.00 equiv). The resulting solution was stirred overnight at 70 C in an oil bath. The reaction mixture was cooled. The resulting solution was extracted with dichloromethane and the organic layers were combined. The solution was dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel column (ethyl acetate/petroleum ether) to afford l-(benzyloxy)-4-[2-(2- bromoethoxy)ethoxy]benzene (6.67g, 76%) as a white solid. LC/MS (ESI) m/z: 350.05 [M+1] +.

Reference： [1]Patent: WO2018/140809,2018,A1 .Location in patent: Paragraph 00438; 00652; 00653; 00654
[2]Bioorganic and Medicinal Chemistry Letters,1996,vol. 6,p. 2491 - 2494

14
[ 103-16-2 ]
[ 106-93-4 ]
[ 3351-59-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate; In acetonitrile; at 100℃;	Potassium carbonate (17.3 g, 125 mmol, 2.5 eq.) was added to a mixture of 4-benzyloxyphenol la (10 g, 50 mmol, 1 eq.) in MeCN (50 ml) and dibromoethane (26 ml, 300 mmol, 6 eq.). The resulting heterogeneous mixture was stirred overnight at 100C. After cooling down to room temperature, ethyl acetate was added and the mixture was filtered over a pad of Celite. The cake was washed with ethyl acetate and the filtrate was concentrated to dryness. The crude mixture was purified by automated silica gel chromatography (from 5% to 15% EtOAc in heptanes) to afford product lb as a bright white solid (12.1 g, 79% yield). 1HNMR: (300 MHz, CHLOROFORM-d) 7.25- 7.42 (m, 5 H) 6.81 - 6.97 (m, 4 H) 5.02 (s, 2 H) 4.24 (t, 2 H) 3.61 (t, 2 H).
71.1%	With potassium hydroxide; In ethanol; for 24h;Reflux;	To a solution of dibromoethane (56.4 g, 0.3 mol), KOH (10 g, 0.18mol) in 150 mL EtOH was added to 2a (30 g, 0.15 mol). The resulting solution was heated under reflux and the progress ofthe reaction monitored by TLC (acetone/petroleum ether 1:2 silica gel). After disappearance of the starting material (about 24 h), the remaining solids were removed by filtration and filtrate was cooled to give white solids. The solids were recrystallized in ethanol to yield 2b, white solid, yields: 71.1 %. m.p.: 79-80C. 1H NMR (300 MHz, CDCl3) delta (ppm): 7.43-7.32 (m, 5H,C6H5), 6.93-6.84 (m, 4H, C6H4), 5.02 (s, 2H, PhCH2O), 4.26-4.22 (t, 2H, OCH2CH2Br), 3.63-3.59 (t, 2H, BrCH2CH2O).
64%		A mixture of 4-benzyloxy-phenol 85.5 (1 equiv.) and NaH in anhydrous dimethylformamide was stirred at RT for 15 min under argon. To this mixture was added 1 ,2-dibromoethane (1.5 equiv.) and stirring was continued at 80C for 6 hours. The reaction mixture was cooled to RT, diluted with water and extracted with diethyl ether. The ethereal layer was washed with water and brine, dried (MgSO4), and concentrated under reduced pressure. Purification by flash column chromatography on silica gel (diethyl ether-hexane) gave product 86.5 in 64% yield.

63%	With potassium carbonate; In acetonitrile; for 96h;Heating / reflux;	To a stirring solution of 4-benzyloxyphenol (72 g, 359.6 mmol) in CH3CN (600 mL) was added dibromoethane (155 mL, 1.80 mol) and K2CO3 (105 g, 759.9 mmol). This brown suspension was heated at reflux and allowed to stir for 96 h. The resulting suspension was cooled to room temperature, diluted with acetone (250 mL), and filtered through diatomaceous earth, which was then rinsed with additional acetone. The filtrate was concentrated under reduced pressure. The resulting oil was dissolved in CH3OH (500 mL), and the solution was stirred for 2 h. The title compound was obtained by filtration and air-dried to give 70 g (228 mmol, 63% yield) as a tan solid. 1H NMR (400 MHz, CDCl3): 7.60-7.30 (m, 5H), 6.88 (d, J=8.4, 2H), 6.80 (d, J=8.4, 2H), 4.70 (s, 2H), 3.79 (t, J=5.8, 2H), 3.07 (t, J=5.8, 2H).
63%		EXAMPLE 1; 2- (4-BENZYLOXY-PHENOXY)-ETHYL bromide; To a stirring solution of 4-benzyloxyphenol (72 g, 359.6 MMOL) in CH3CN (600 mL) was added dibromoethane (155 mL, 1.80 mol) and K2CO3 (105 g, 759.9 MMOL). This brown suspension was heated at reflux and allowed to stir for 96 h. The resulting suspension was cooled to room temperature, diluted with acetone (250 mL), and filtered through diatomaceous earth, which was then rinsed with additional acetone. The filtrate was concentrated under reduced pressure. The resulting oil was dissolved in CH30H (500 ML), and the solution was stirred for 2 h. The title compound was obtained by filtration and air-dried to give 70 g (228 mmol, 63% yield) as a tan SOLID. 1H NMR (400 MHz, CDC13) : 7.60-7. 30 (m, 5H), 6.88 (d, J = 8.4, 2H), 6.80 (d, J = 8.4, 2H), 4.70 (s, 2H), 3.79 (t, J = 5.8, 2H), 3.07 (t, J = 5.8, 2H)
63%	With potassium carbonate; In acetonitrile; for 96h;Heating / reflux;	Example 1 2-(4-Benzyloxy-phenoxy)-ethyl bromide To a stirred solution of 4-benzyloxyphenol (72 g, 359.6 mmol) in CH3CN (600 mL) was added dibromoethane (155 mL, 1.80 mol) and K2CO3 (105 g, 759.9 mmol). This brown suspension was heated at reflux and allowed to stir for 96 h. The resulting suspension was cooled to room temperature (rt), diluted with acetone (250 mL), and filtered through diatomaceous earth, which was then rinsed with additional acetone. The filtrate was concentrated. The resulting oil was dissolved in CH3OH (500 mL), and the solution was stirred for 2 h. The title compound was obtained by filtration and air-dried to give 70 g (228 mmol, 63%) as a tan solid. 1H NMR (400 MHz, CDCl3): 7.60-7.30 (m, 5H), 6.88 (d, J=8.4, 2H), 6.80 (d, J=8.4, 2H), 4.70 (s, 2H), 3.79 (t, J=5.8, 2H), 3.07 (t, J=5.8, 2H).
	With potassium carbonate; In hexane; ethyl acetate; acetonitrile;	A) 2-(4-Benzyloxyphenoxy)ethyl bromide. A mixture of 4-(benzyloxy)phenol (10 g, 0.05 mol), potassium carbonate (17.3 g, 0.125 mol) in 50 mL of acetonitrile and 21.6 mL of 1,2-dibromoethane was allowed to reflux for 24 h. The inorganic salt was removed through a short column of silica gel and washed with ethyl acetate (3*25 mL). The combined flitrate was evaporated in vacuo to give a crude mixture, which was purified by flash chromatography (5% EtOAc in hexane), giving 12 g (79%) of the bromide as a white solid. mp 75-77 C. 1 H NMR (CDCl3) 3.611 (t, J=6.2 Hz, 2 H), 4.242 (t, J=6.2 Hz, 2 H), 5.021 (s, 2 H), 6.869 (m, 4 H), 7.381 (m, 5 H).

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2993 - 3000
[2]Patent: WO2018/141854,2018,A1 .Location in patent: Page/Page column 23
[3]Asian Journal of Chemistry,2016,vol. 28,p. 551 - 554
[4]Patent: WO2009/52319,2009,A1 .Location in patent: Page/Page column 135
[5]Patent: US2008/194630,2008,A1 .Location in patent: Page/Page column 28
[6]Journal of Medicinal Chemistry,2008,vol. 51,p. 4150 - 4169
[7]Patent: WO2005/12296,2005,A1 .Location in patent: Page/Page column 76
[8]Patent: US2006/223792,2006,A1 .Location in patent: Page/Page column 22
[9]Bioorganic and Medicinal Chemistry Letters,1996,vol. 6,p. 2491 - 2494
[10]Patent: US6124323,2000,A

15
[ 103-16-2 ]
[ 115314-14-2 ]
[ 122797-04-0 ]

Yield	Reaction Conditions	Operation in experiment
65%		An appropriate phenol (7.7 mM) is added to a suspension of HNa (185 mg, 7.7 mM) in anhydrous N,N-dimethylformamide (40 ml), maintained at room temperature in agitation and in a nitrogen atmosphere. When the compound is clear, a solution of (S)-glycidyl m-nitrobenzenesulfonate (2 g, 7.7 mM) in anhydrous N,N-dimethylformamide (40 ml) is added dropwise. The mixture is left in agitation at room temperature until completion of the reaction. It is then diluted with water and extracted four times with ethyl acetate. The combined organic phases are washed three times with a saturated solution of Na2CO3, then with water, and dried over Na2SO4 and the solvent is removed under vacuum.; Time of the reaction: 21 h. P.f.: 77.2-78.6 C. (ethyl acetate/hexane), white solid. Yield=65%. [alpha]D=+2.87 (c 1.01 CH Cl3). FT-IR (KBr): 3104, 3062, 3035, 3010, 2908, 2876, 2861, 2918, 1510, 1452, 1466, 1386, 1337, 1288, 1239, 1225, 1136, 1120, 1041, 1030, 1018, 995, 918, 860, 826, 782, 733, 692 cm-1. 1NMRs (300 MHz CD Cl3, delta): 2.73-2.76 (dd, J=2.7 Hz and 4.9 Hz, 1H, CH2 epoxide), 2.88-2.91 (dd, J=4.1 Hz and 4.9 Hz, 1H, CH2 epoxide), 3.31-3.36 (m, 1H, CH epoxide), 3.89-3.94 (dd, J=5.5 Hz and 11.0 Hz, 1H, CH2O), 4.15-4.19 (dd, J=3.3 Hz and 11.0 Hz, 1H, CH2O), 5.02 (s, 2H, CH2C6H5), 6.82-6.94 (m, 4H, aromatic protons), 7.29-7.44 (m, 5H, aromatic protons). 13C NMRs (75 MHz CDCl3, delta): 44.97, 50.49, 69.70, 70.87, 115.91, 116.05, 127.72, 128.15, 128.79, 137.43, 153.08, 153.60. GC-MS (70 eV) m/z (int. rel.): 256 (M+, 22), 165 (4), 109 (2), 91 (100), 65 (8), 57 (7). Anal. (C16H16O3): Cal.: C, 74.98; H, 6.29. Found: C, 74.80; H, 6.33.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 509 - 513
[2]Patent: US2010/75977,2010,A1 .Location in patent: Page/Page column 12
[3]Medicinal Chemistry Research,2000,vol. 10,p. 164 - 177
[4]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 1101 - 1106

16
[ 103-16-2 ]
[ 115314-14-2 ]
[ 222422-05-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 1101 - 1106
[2]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 509 - 513

17
[ 103-16-2 ]
[ 2312-15-4 ]
[ 124501-19-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With dmap; dicyclohexyl-carbodiimide In dichloromethane
	With dmap; dicyclohexyl-carbodiimide In dichloromethane for 24h; Ambient temperature;

Reference： [1]Shivakumar, Kilingaru I.; Pociecha, Damian; Szczytko, Jacek; Kapuściński, Szymon; Monobe, Hirosato; Kaszyński, Piotr [Journal of Materials Chemistry C, 2020, vol. 8, # 3, p. 1083 - 1088]
[2]Rowe, Kathryn E.; Bruce, Duncan W. [Journal of Materials Chemistry, 1998, vol. 8, # 2, p. 331 - 341]

18
[ 103-16-2 ]
[ 117241-31-3 ]
[ 934824-23-4 ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 1674 - 1691
[2]Journal of Materials Chemistry,1998,vol. 8,p. 331 - 341

19
[ 5631-96-9 ]
[ 103-16-2 ]
[ 205381-75-5 ]

Reference： [1]Canadian Journal of Chemistry,1998,vol. 76,p. 1429 - 1436

20
[ 103-16-2 ]
[ 63558-65-6 ]
4-(4-benzyloxy-phenoxy)-5-iodo-pyrimidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 8235 - 8239

21
[ 89539-54-8 ]
[ 103-16-2 ]
[ 532429-02-0 ]

Reference： [1]Synthetic Communications,2003,vol. 33,p. 1081 - 1086

22
[ 103-16-2 ]
[ 83902-02-7 ]
2-(4-Benzyloxy-phenoxymethyl)-1,3-dimethyl-benzene [ No CAS ]

Reference： [1]Synthesis,2004,p. 692 - 700

23
[ 31255-26-2 ]
[ 103-16-2 ]
[ 744251-98-7 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium carbonate In acetone for 36h; Heating;
40%	With potassium carbonate In acetonitrile for 36h; Heating;

Reference： [1]Feng, Dai-Jun; Li, Xiao-Qiang; Wang, Xiao-Zhong; Jiang, Xi-Kui; Li, Zhan-Ting [Tetrahedron, 2004, vol. 60, # 29, p. 6137 - 6144]
[2]Li, Xiao-Qiang; Feng, Dai-Jun; Jiang, Xi-Kui; Li, Zhan-Ting [Tetrahedron, 2004, vol. 60, # 37, p. 8275 - 8284]

24
[ 103-16-2 ]
[ 6226-25-1 ]
[ 200956-20-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With caesium carbonate; In acetonitrile; at 85℃; for 3h;Inert atmosphere;	In a high pressure flask was charged 4-(benzyloxy)phenol (0.30 g, 1.5 mmol), cesium carbonate (0.49 g, 1.5 mmol), <strong>[6226-25-1]2,2,2-trifluoroethyl trifluoromethanesulfonate</strong> (0.32 mL, 2.25 mmol) and dry acetonitrile (7.5 mL). The flask was flushed with N2 for 5 minutes, capped and heated at 85 C (bath temperature) for 3.0 h. After cooling to r.t., the solid was filtered off and the filtrate was diluted with ethyl acetate and washed with brine three times. The organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (10% ethyl acetate/hexanes) to give a white solid

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 7080 - 7082
[2]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 3347 - 3351

25
[ 3196-15-4 ]
[ 103-16-2 ]
[ 653563-74-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With caesium carbonate; In acetonitrile; for 20h;Reflux;	A mixture of 4-benzyloxyphenol (30g, 0. [15MOL),] cesium carbonate [(58.] 6g, 0. [18MOL)] and <strong>[3196-15-4]methyl 2-bromobutanoate</strong> (40.7g, 0. [22MOL)] in CH3CN (350mL) was kept at reflux for 20hr. After cooling, the mixture was filtered and concentrated under reduced pressure and chromatographed over silica gel using [ACOET/HEXANES] to give the title compound [41. OG (91%).] [1H-NMR] [(400MHZ,] [CDCL3)] : [8] 7.45-7. 31 (m, [7H),] 6.9 (d, 2H, J=9.2Hz), 6.85 (d, 2H, J=9.2Hz), 5.02 (s 2H), 4.45 (t, 1H, J=6.3Hz), 3.76 (s, 3H), 1.98 (dq, 2H, J=7.4, 6.3Hz), 1.08 (t, 3H, J=7.4Hz).

Reference： [1]Patent: WO2004/10992,2004,A1 .Location in patent: Page/Page column 30; 31
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1673 - 1678

26
[ 103-16-2 ]
[ 96-32-2 ]
[ 81466-35-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 24h;	General procedure: To a stirred solution of phenol (1 mmol) in DMF (3 mL) were added methyl bromoacetate (0.1 mL, 1 mmol) and K2CO3 (207 mg, 1.5 mmol), and the resulting mixture was heated at 80 C for 24 h. After cooling, the reaction mixture was diluted with EtOAc, and filtered by celite pad. The filtrate was evaporated, and the residue was chromatographed on silica gel (15 g, hexane : acetone = 50 : 1 ~ 40 : 1) to give corresponding ether.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 3732 - 3735
[2]Cell Chemical Biology,2020,vol. 27,p. 41 - 46
[3]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1673 - 1678

27
[ 103-16-2 ]
[ 17702-83-9 ]
N-[8-(4-benzyloxyphenoxy)-1-octyl]-phthalimide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2612 - 2621

28
[ 99586-65-9 ]
[ 103-16-2 ]
[ 952490-94-7 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4351 - 4373

29
[ 103-16-2 ]
[ 65343-67-1 ]

Reference： [1]Journal of Organic Chemistry,2003,vol. 68,p. 7234 - 7242
[2]Organic and Biomolecular Chemistry,2018,vol. 16,p. 6460 - 6469

30
[ 103-16-2 ]
[ 123-31-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With palladium 10% on activated carbon; hydrogen; In methanol; at 50℃; under 750.075 Torr;Flow reactor;	General procedure: A solution of the substrates possessing reducible functional groups (1mmol) within the molecule in MeOH (20mL) was flowed at 1mL/min into the catalyst-packed cartridge (10% Pd/C, 10% Pd/HP20, 0.5% Pd/MS3A, or 0.3% Pd/BN; 30mm long-cartridge, ca. 0.3mL volume) under 1, 50, or 80bar hydrogen gas at 25, 50, 75, or 100C using H-Cube (ThalesNano Nanotechnology Inc.). Catalyst cartridges were filled with 10% Pd/C (99.4mg), 10% Pd/HP20 (101.4mg), 0.5% Pd/MS3A (99.6mg), and 0.3% Pd/BN (99.7mg). The reaction mixture was passed through the catalyst cartridge once and MeOH (the carrier solvent) was concentrated in vacuo to give an analytically pure product. The obtained product was identified by 1H NMR measurement.
100%	With hydrogen; In methanol; at 20℃; under 760.051 Torr; for 18h;	General procedure: A mixture of the substrate (0.250mmol) and catalyst [8% Pd/CR11 (3.3mg, 2.50mumol) or 9% Pd/CR20 (3.0mg, 2.50mumol)] in MeOH (1mL) was stirred under an H2 atmosphere (balloon) at room temperature. After a specific time, the mixture was filtered through a membrane filter (0.45 or 0.2mum), and the filtrate was concentrated in vacuo to give the corresponding spectrometrically-pure reduced product. If the reaction was not completed, the temperature was raised to 40 or 50C. If the reaction was still incomplete, the H2 pressure was increased to 3 or 5atm. All the products were known, and the 1H NMR spectral data of the products were identical to those in the literature (see Supplementary data).
	With formic acid; for 3h;Heating / reflux;	<strong>[103-16-2]Hydroquinone monobenzyl ether</strong> (1.5 g) was dissolved in 85% methanoic acid (100 ml) and the solution was heated with continous stirring. After refluxing for about 3 hours, analysis by 1H-NMR spectroscopy revealed that ether cleavage had taken place to produce a solution of hydroquinone in 85% methanoic acid.

Reference： [1]Tetrahedron,2014,vol. 70,p. 4790 - 4798
[2]Tetrahedron,2015,vol. 71,p. 6499 - 6505
[3]Advanced Synthesis and Catalysis,2017,vol. 359,p. 2269 - 2279
[4]Synthesis,1982,p. 987 - 988
[5]Patent: US2004/10166,2004,A1 .Location in patent: Page 4

31
[ 103-16-2 ]
[ 627-18-9 ]
[ 164396-35-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium hydroxide; tetrabutylammomium bromide In water; toluene at 60℃; for 17h;	1 Example 1 A mixture of 1.15 g of 3-bromopropanol, 7.5 g of toluene and 0.12 g of tetra-n-butylammonium bromide was heated to 60°C, and thereto was added a slurry solution of 1.5 g of 4-(benzyloxy)phenol, 7.5 g of water and 1.22 g of a 27% aqueous sodium hydroxide solution with stirring. After addition, the mixture was stirred at 60°C for 17 hours. In this period, 0.40 g of 3-bromopropanol and 0.40 g of a 27% aqueous sodium hydroxide solution were further added thereto at the time point of 13 hours. Subsequently, the reaction mixture was cooled to 20°C. After 3.0 g of a 20% aqueous sulfuric acid solution and 15.0 g of toluene were added thereto, the mixture was stirred and then separated. The obtained organic layer was washed with 7.5 g of a 1% aqueous sodium hydroxide solution once and with 7.5 g of water once, and concentrated under reduced pressure to give 2.0 g of 3-(4-benzyloxy)phenoxy)-1-propyl alcohol (purity: 93%, yield: 94%).
	With potassium carbonate; potassium iodide In DMF (N,N-dimethyl-formamide) at 80℃; for 5h;

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - EP2036878, 2009, A1 Location in patent: Page/Page column 10-11
[2]Current Patent Assignee: DIC CORP. - EP1174412, 2002, A1 Location in patent: Page 79

32
[ 103-16-2 ]
[ 2008-75-5 ]
[ 182133-34-2 ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium carbonate; caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 72h;	To a mixture of 4-(benzyloxy)phenol (24.6 g, 123 mmol) and 1-(2-chloroethyl)piperidine hydrochloride (20.6 g, 112 mmol) in DMF (175 mL) was added K2CO3 (25 g, 181 mmol) and Cs2CO3 (40 g, 123 mmol). The reaction mixture was stirred for 3 days at room temperature. To the mixture was added H2O (300 mL) and CH2Cl2. The organic layer was washed with 10% NaOH then brine, dried (MgSO4), filtered, and concentrated under reduced pressure to give 33 g of a clear, dark purple liquid. The liquid was purified on SiO2 (300 g; 0-50% ethyl acetate/hexanes) to give 23.4 g (67% yield) of a light yellow solid. TLC (SiO2, 50% hexanes/ethyl acetate): Rf=0.11. MS (ESI): mass calculated for C20H25NO2, 311.19; m/z found, 312.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.50-7.26 (m, 5H), 6.91 (d, J=9.2, 2H,), 6.85 (d, J=9.2, 2H), 5.02 (s, 2H), 4.06 (t, J=6.1, 2H), 2.76 (t, J=6.1, 2H), 2.51 (br s, 4H), 1.65-1.55 (m, 4H), 1.45 (br s, 2H).
67%	With potassium carbonate; caesium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 72h;	EXAMPLE 11; 2-{4-[4-(2-Piperidin-1-yl-ethoxy)-phenoxy]-benzooxazole; A. 1-(2-(4-BENZVLOXV-PHENOXY)-ETHVLL-PIPERIDINE; To a mixture of 4- (BENZYLOXY) PHENOL (24.6 g, 123 MMOL) and 1- (2-CHLOROETHYL) PIPERIDINE hydrochloride (20.6 g, 112 MMOL) in DMF (175 mL) was added K2CO3 (25 g, 181 MMOL) and Cs2CO3 (40 g, 123 MMOL). The reaction mixture was stirred for 3 days at room temperature. To the mixture was added H20 (300 mL) and CH2CI2. The organic layer was washed with 10% NAOH then brine, dried (MGS04), filtered, and concentrated under reduced pressure to give 33 g of a clear, dark purple liquid. The liquid was purified on SI02 (300 g; 0-50% ethyl acetate/hexanes) to give 23.4 g (67% yield) of a light yellow solid. TLC (SI02, 50% hexanes/ethyl acetate): Rf = 0.11. MS (ESI) : mass calculated for C20H25NO2, 311.19 ; m/z found, 312.2 [M+H] +. 1H NMR (400 MHz, CDCl3) : 7.50-7. 26 (m, 5H), 6.91 (d, J = 9.2, 2H, ), 6.85 (d, J = 9.2, 2H), 5.02 (s, 2H), 4.06 (t, J = 6.1, 2H), 2.76 (t, J = 6.1, 2H), 2.51 (br s, 4H), 1.65-1. 55 (m, 4H), 1.45 (BR S, 2H)
67%	With potassium carbonate; caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 72h;	A. 1-[2-(4-Benzyloxy-phenoxy)-ethyl]-piperidine. To a mixture of 4-(benzyloxy)phenol (24.6 g, 123 mmol) and 1-(2-chloroethyl)piperidine hydrochloride (20.6 g, 112 mmol) in DMF (175 mL) was added K2CO3 (25 g, 181 mmol) and Cs2CO3 (40 g, 123 mmol). The reaction mixture was stirred for 3 d at rt. To the mixture was added H2O (300 mL) and CH2Cl2. The organic layer was separated and washed sequentially with 10% aq. NaOH and brine, dried (MgSO4), filtered, and concentrated to give 33 g of a clear, dark purple liquid. The liquid was purified on SiO2 (300 g; 0-50% EtOAc/hexanes) to give 23.4 g (67%) of a light yellow solid. TLC (SiO2, 50% hexanes/EtOAc): Rf=0.11. MS (ESI): mass calculated for C20H25NO2, 311.19; m/z found, 312.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.50-7.26 (m, 5H), 6.91 (d, J=9.2, 2H), 6.85 (d, J=9.2, 2H), 5.02 (s, 2H), 4.06 (t, J=6.1, 2H), 2.76 (t, J=6.1, 2H), 2.51 (br s, 4H), 1.65-1.55 (m, 4H), 1.45 (br s, 2H).

Reference： [1]Patent: US2008/194630,2008,A1 .Location in patent: Page/Page column 30
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 4150 - 4169
[3]Patent: WO2005/12296,2005,A1 .Location in patent: Page/Page column 81-82
[4]Patent: US2006/223792,2006,A1 .Location in patent: Page/Page column 27

33
[ 549494-33-9 ]
[ 103-16-2 ]
[ 549494-34-0 ]

Yield	Reaction Conditions	Operation in experiment
61%	With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene; at 55℃;	TRIPHENYLPHOSPHINE (2.4g, 9mmol) was added to a solution of methyl 2-CHLORO-3- [4- (2- hydroxyethyl) phenyl] propanoate (2. 1G, 8. 5MMOL) AND 4- (BENZYLOXY) phenol (1.7g, 8MMOL) in 20ml toluene under nitrogen atmosphere. The solution was warmed to 55C and diisopropyl azodicarboxylate (1. 8G, 9MMOL) was added. The reaction mixture was stirred at 55C overnight. The mixture was allowed to cool and the solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography using a 80: 20 mixture of heptane and EtOAc as eluent to yield 2.28g of the desired product (yield 61%) as colourless crystals. 1HNMR (400MHZ, CDC13) : 3.05 (t, 2H), 3.16 (dd, 1H), 3.36 (dd, 1H), 3.75 (s, 3H), 4.12 (t, 2H), 4.45 (t, 1H), 5.01 (s, 2H), 6. 82 (M, 2H), 6.90 (m, 2H), 7.13-7. 27 (M, 4H), 7. 29- 7. 47 (M, 5H)
61%	With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene;	TRIPHENYLPHOSPHINE (2.4g, 9mmol) was added to a solution of methyl 2-CHLORO-3- [4- (2- hydroxyethyl) phenyl] propanoate (2. 1G, 8. 5MMOL) and 4- (benzyloxy) phenol (1.7g, 8mmol) in 20ML toluene under nitrogen atmosphere. The solution was warmed to 55C and diisopropyl azodicarboxylate (1. 8g, 9MMOL) was added. The reaction mixture was stirred at 55C overnight. The mixture was allowed to cool and the solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography using a 80: 20 mixture of heptane and EtOAc as eluent to yield 2.28g of the desired product (yield 61%) as colourless crystals. 1HNMR (400MHZ, CDC13) : 3.05 (t, 2H), 3.16 (dd, 1H), 3.36 (dd, 1H), 3.75 (s, 3H), 4.12 (t, 2H), 4.45 (t, 1H), 5.01 (s, 2H), 6.82 (M, 2H), 6.90 (M, 2H), 7.13-7. 27 (M, 4H), 7. 29- 7. 47 (M, 5H).
61%	With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene; at 55℃;	Triphenylphosphine (2.4g, 9mmol) was added to a solution of methyl 2-CHLORO-3- [4- (2- hydroxyethyl) phenyl] propanoate (2. 1g, 8. 5MMOL) and 4- (BENZYLOXY) phenol (1.7g, 8MMOL) in 20ML toluene under nitrogen atmosphere. The solution was warmed to 55C and diisopropyl azodicarboxylate (1.8g, 9MMOL) was added. The reaction mixture was stirred at 55C overnight. The mixture was allowed to cool and the solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography using a 80: 20 mixture of heptane and EtOAc as eluent to yield 2.28g of the desired product (yield 61%) as colourless crystals.

61%	With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene;	TRIPHENYLPHOSPHINE (2.4g, 9mmol) was added to a solution of methyl 2-CHLORO-3- [4- (2- hydroxyethyl) phenyl] propanoate (2. 1G, 8. 5MMOL) and 4- (benzyloxy) phenol (1.7g, 8mmol) in 20ML toluene under nitrogen atmosphere. The solution was warmed to 55C and diisopropyl azodicarboxylate (1. 8g, 9MMOL) was added. The reaction mixture was stirred at 55C overnight. The mixture was allowed to cool and the solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography using a 80: 20 mixture of heptane and EtOAc as eluent to yield 2.28g of the desired product (yield 61%) as colourless crystals. 1HNMR (400MHZ, CDC13) : 3.05 (t, 2H), 3.16 (dd, 1H), 3.36 (dd, 1H), 3.75 (s, 3H), 4.12 (t, 2H), 4.45 (t, 1H), 5.01 (s, 2H), 6.82 (M, 2H), 6.90 (M, 2H), 7.13-7. 27 (M, 4H), 7. 29- 7. 47 (M, 5H).
57%	With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene; at 55℃;	Methyl 2-CHLORO-3- [4- (2-HYDROXYETHYL) phenyl] propanoate (12.2g, 50. 6MMOL) and 4- (benzyloxy) phenol (10. LG, 50. 6MMOL) was dissolved in 350ml dry toluene. TRIPHENYLPHOSPHINE (14.6g, 55. 6MMOL) was added. The mixture was heated to 55C and diisopropyl azodicarboxylate (11. 2g, 55. 6MMOL) was added. The reaction mixture was stirred overnight at 55C. The reaction was followed on thin layer chromatography (HEPTANE/ETHYL acetate (80: 20) ). The solvent was evaporated and diethyl ether was added. The triphenylphosphine oxide was filtered off, the solvent was evaporated and the residue was purified by flash chromatography using toluene as eluent to yield 12.3g of the desired product (57% yield) as white crystals. 1HNMR (400MHZ, CDC13) : 3.05 (t, 2H), 3.16 (dd, 1H), 3.36 (dd, 1H), 3.75 (s, 3H), 4.11 (t, 2H), 4.45 (t, 1H), 5.02 (s, 2H), 6.80-6. 84 (M, 2H), 6.88-6. 91 (M, 2H), 7.14-7. 28 (M, 4H), 7.29-7. 44 (M, 5H)

Reference： [1]Patent: WO2004/113282,2004,A1 .Location in patent: Page 25-26
[2]Patent: WO2004/113283,2004,A1 .Location in patent: Page/Page column 23
[3]Patent: WO2004/113285,2004,A1 .Location in patent: Page 5
[4]Patent: WO2004/113284,2004,A1 .Location in patent: Page/Page column 21
[5]Patent: WO2004/113282,2004,A1 .Location in patent: Page 29

34
[ 103-16-2 ]
[ 26487-67-2 ]
C₂₀H₂₅NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; DMF (N,N-dimethyl-formamide); at 0 - 60℃; for 0.5h;	Add sodium hydride (18 g, 0.45 mol) into a solution of 4-benzyloxylphenol (41 g, 0.20 mol) and 2- (hexamethyleneimino) ethyl chloride hydrochloride (44 g, 0.22 mmol) in THF (600 mL) and DMF (100 mL) at room temperature. Heat to 60°C for 30 minutes. Pour the solution into ice and water. Dilute with ethyl acetate (500 mL) and separate layers. Dry the organic layer with magnesium sulfate, filter and concentrate under reduced pressure to give brown oil. Dissolve the oil in ethyl acetate (500 mL) and methanol (500 mL). Add ammonium formate (100 g, 1.59 mol) and palladium on carbon (10 g, 9.4 mmol). Heat the mixture to reflux for 30 minutes. Add ammonium formate (100 g, 1.59 mol) and palladium on carbon (10 g, 9.4 mmol). Heat the reaction mixture for 30 minutes. Filter the supension through a pad of celite and elute with ethyl acetate (500 mL). Evaporate solvent under reduced pressure and add water (100 mL). Dilute the mixture with ethyl acetate (500 mL) and separate layers. Wash the organic layer with saturated sodium bicarbonate solution (2 x 200 mL), dry with magnesium sulfate, filter and evaporate solvent under reduced pressure to give 31 g (64 percent) of4- (2-azepan-l-yl- ethoxy)-phenol. Combine 2-benzyloxy-1-bromo-6-methoxy-naphthalene (31 g, 90 mmol), 4- (2- azepan-l-yl-ethoxy)-phenol (31 g, 132 mmol), copper bronze (12 g, 189 mmol), potassium carbonate (25 g, 181 mmol) and pyridine (400 mL). Heat the reaction mixture to reflux for 85 hours. Cool and filter the residue with celite and elute with methanol and methylene chloride (500 mL, Vu = 1 : 5). Evaporate solvent under reduced pressure and chromatograph the residue on a silica gel column eluting the material with a step gradient of methanol/dichloromethane (0 to 10percent) to get 19 g (43percent) of 1- {2- [4- (2-benzyloxy-6- meCoxy-naphthalen-l-yloxy)-phenoxyl-ethyl}-azepane. Dissolve 1- {2- [4- (2-benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]-ethyl}- azepane (19 g, 38 mmol) in ethyl acetate (500 mL) and methanol (600 mL). Heat the mixture to obtain a clear solution. Cool to room temperature. Add ammonium formate (30 g, 476 mmol) and palladium on carbon (2 g, 1. 9 mmol). Heat to reflux for 30 minutes. Add ammonium formate (7 g, 111 mmol) and palladium on carbon (0.7 g, 0.7 mmol). Heat to reflux for 30 minutes. Filter the supension through a pad of celite and elute with ethyl acetate (500 mL). Evaporate solvent under reduced pressure and add water (100 mL). Dilute the mixture with ethyl acetate (500 mL) and separate layers. Wash the organic layer with saturated sodium bicarbonate solution (2 x 200 mL), dry with magnesium sulfate, filter and evaporate solvent under reduced pressure to give 15.1 g (97percent) of 1- [4- (2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-napbthalen-2-ol. Add trifluoromethanesulfonic anhydride (7 mL, 42 mmol) into a solution of 1- [4- (2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-ol (15 g, 37 mmol), triethylamine (20 mL) and methylene chloride (500 mL) at-50°C. Warm the reaction mixture to room temperature and stir for 1 hour at that temperature. Cool the reaction mixture to-78°C and add brine (20 mL). Warm the reaction to room temperature. Separate layer and wash the organic layer with saturated sodium bicarbonate solution (100 mL) and brine. Dry the organic layer with magnesium sulfate, filter and evaporate solvent under reduced pressure. Chromatograph the residue on a silica gel column eluting the material with a step gradient of methanol/dichloromethane (0 to 10percent) to get 20 g (99percent) of trifluoro-methanesulfonic acid 1- [4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy- naphthalen-2-yl ester.

Reference： [1]Patent: WO2005/73204,2005,A1 .Location in patent: Page/Page column 26-28

35
[ 356783-16-9 ]
[ 103-16-2 ]
[ 356783-23-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N-methyl-acetamide; di-isopropyl ether; water; ethyl acetate;	REFERENTIAL EXAMPLE II-12 In 25 mL of dimethylformamide was dissolved 2.5 g of <strong>[356783-16-9]3,6-dichloro-2-pyrazinecarbonitrile</strong>. After adding 3.2 g of 4-(benzyloxy)phenol and 3.0 g of potassium carbonate, the mixture was stirred at room temperature for one hour. A mixture of 25 ml of ethyl acetate and 100 mL of water was added to the reaction mixture, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Diisopropyl ether was added to the residue, the insoluble matter was filtered off, and the filtrate was concentrated. The residue thus obtained was washed with n-hexane to obtain 3.84 g of 3-[(4-(benzyloxy)phenoxy)]-6-chloro-2-pyrazinecarbonitrile as a light brown-colored solid product. R (KBr) cm-1: 2238 H-NMR (CDCl3) delta: 5.12(2H,s), 7.03-7.48(9H,m), 8.65(1H,s)

Reference： [1]Patent: US2003/130213,2003,A1

36
[ 103-16-2 ]
[ 113826-06-5 ]
[ 122797-04-0 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	(2S)-2-[(4-Benzyloxyphenoxy)methyl]oxirane 4-Benzyloxyphenol (15.00 g, 74.91 mmol) in anhydrous N,N-dimethylformamide (50 mL) was added to a solution of sodium hydride (60% dispersion in oil) (2.88 g, 74.9 mmol) in N,N-dimethylformamide (50 mL). The solution was stirred for 30 minutes and (S)-(+)-glycidyl 4-methylbenzenesulfonate (17.12, 75.0 mmol) was added. The mixture was heated to 80 C. for 2 hours. The solvent was removed and the residue partitioned between diethyl ether and water. The organic phase was washed with brine and dried over anhydrous magnesium sulfate. The solution was filtered and the solvent evaporated to dryness in vacuo. To yield the title compound as a white solid (13.6 g, 53.3 mmol). MS (EI, m/z): 256 [M]+

Reference： [1]Patent: US2002/28832,2002,A1

37
[ 103-16-2 ]
[ 55676-22-7 ]
[ 257609-07-7 ]

Yield	Reaction Conditions	Operation in experiment
	In water;	Reference Example 9 Synthesis of 6-(4-benzyloxyphenoxy)-3-acetylpyridine Dried DMF solution (50 ml) of sodium hydride (60% in oil, 7.24 g, 181 mmol) was cooled with ice in nitrogen atmosphere, dried DMF solution (50 ml) of hydroquinone monobenzyl ether (36.2 g, 181 mmol) was dropped into the above solution spending 10 minutes under ice cooling and the mixture was stirred for 1.5 hours under ice cooling. Dried DMF solution (110 ml) of 6-chloro-3-acetylpyridine (26.7 g, 172 mmol) was dropped into the above mixture spending 15 minutes and stirred for 2 hours under ice cooling. After completing the reaction, the reaction liquid was acidified with 6N hydrochloric acid, added with water, extracted with ethyl acetate, washed with water (400 ml*3), dried with magnesium sulfate and concentrated. The residue was recrystallized from 2-propanol (300 ml) to obtain the subject compound (43.3 g, 136 mmol). The result of 1H-NMR was consistent with the above structure. Yield: 75% 1H-NMR (CDCl3); delta8.76 (d, 1H, J=2.64 Hz), 8.24 (dd, 1H, J=2.64, 8.58 Hz), 7.46-7.31 (m, 5H), 7.10-7.00 (m, 4H), 6.94 (d, 1H, J=8.58 Hz), 5.08 (s, 2H), 2.56 (s, 3H).

Reference： [1]Patent: US6649656,2003,B1

38
[ 7342-82-7 ]
[ 103-16-2 ]
[ 1317-39-1 ]
[3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene [3-(4-benzyloxy)phenoxy]benzo[b]thiophene [ No CAS ]
[ 95-15-8 ]

Yield	Reaction Conditions	Operation in experiment
	In 2,3,5-trimethyl-pyridine;	PREPARATION 1 Preparation of [3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene [3-(4-benzyloxy)phenoxy]benzo[b]thiophene STR32 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2 was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3*150 mL). The organic was dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C.). The remainder of the material was chromatographed (silicon dioxide, hexanes:ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of [3-(4-benzyloxy)phenoxy]benzo-[b]thiophene as an off-white solid.
	In 2,3,5-trimethyl-pyridine;	Preparation 1 Preparation of [3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene [3-(4-benzyloxy)phenoxy]benzo[b]thiophene STR28 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2 was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3*150 mL). The organic was dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C.). The remainder of the material was chromatographed (silicon dioxide, hexanes: ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of [3-(4-benzyloxy)phenoxy]benzo-[b]thiophene as an off-white solid. mp 84-86 C. 1 H NMR (CDCl3) d 7.91-7.83 (m, 2 H), 7.47-7.34 (m, 7 H), 7.04 (q, JAB =9.0 Hz, 4H), 6.47 (s, 1 H), 5.07 (s, 2H). Anal. Calcd. for C21 H16 O2 S: C, 75.88; H, 4.85. Found: C, 75.75; H, 5.00.

Reference： [1]Patent: US5856339,1999,A
[2]Patent: US5856340,1999,A

39
[ 7342-82-7 ]
[ 103-16-2 ]
[ 1317-39-1 ]
[3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene[3-(4-benzyloxy)phenoxy]benzo[b]thiophene [ No CAS ]
[ 95-15-8 ]

Yield	Reaction Conditions	Operation in experiment
	In 2,3,5-trimethyl-pyridine;	Preparation 1 Preparation of [3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene[3-(4-benzyloxy)phenoxy]benzo[b]thiophene STR28 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2 was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3*150 mL). The organic was dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C.). The remainder of the material was chromatographed (silicon dioxide, hexanes:ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of [3-(4-benzyloxy)phenoxy]benzo-[b]thiophene as an off-white solid. mp 84-86 C. 1 H NMR (CDCl3) d 7.91-7.83 (m, 2H), 7.47-7.34 (m, 7H), 7.04 (q, JAB =9.0 Hz, 4H), 6.47 (s, 1H), 5.07 (s, 2H). Anal. Calcd. for C21 H16 O2 S: C, 75.88; H, 4.85. Found: C, 75.75; H, 5.00.
	In 2,3,5-trimethyl-pyridine;	PREPARATION 1 Preparation of [3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene[3-(4-benzyloxy)phenoxy]benzo[b]thiophene STR31 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 a anhydrous collidine under N2 was added 4-benzyloxyphenol (9.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3*150 mL). The organic was dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C.). The remainder of the material was chromatographed (silicon dioxide, hexanes:ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of [3-(4-benzyloxy)phenoxy]benzo-[b]thiophene as an off-white solid. mp 84-86 C. 1 H NMR (CDCl3) d 7.91-7.83 (m, 2H), 7.47-7.34 (m, 7H), 7.04 (q, JAB =9.0 Hz, 4H), 6.47 (s, 1H), 5.07 (s, 2H). Anal. Calcd. for C21 H16 O2 S: C, 75.88; H, 4.85. Found: C, 75.75; H, 5.00.

Reference： [1]Patent: US5919800,1999,A
[2]Patent: US5998441,1999,A

40
[ 7342-82-7 ]
[ 103-16-2 ]
[ 1317-39-1 ]
[ 176671-90-2 ]
[ 95-15-8 ]

Yield	Reaction Conditions	Operation in experiment
	In 2,4,6-trimethyl-pyridine;	Preparation 1 3-(4-Benzyloxy)phenoxybenzo[b]thiophene STR13 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous 2,4,6-collidine under N2 is added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture is heated to reflux for 24 hours. Upon cooling, the reaction mixture is diluted with ethyl acetate (200 mL) and the crude mixture is filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate is washed with 1N hydrochloric acid (3*150 mL). The organic is dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C.). The remainder of the material is chromatographed (silicon dioxide, hexanes: ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of 3-(4-benzyloxy)phenoxybenzo[b]thiophene as an off-white solid.
	In 2,3,5-trimethyl-pyridine;	[3-(4-benzyloxy)phenoxy]benzo[b]thiophene STR13 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2 was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3*150 mL). The organic was dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C.). The remainder of the material was chromatographed (silicon dioxide, hexanes: ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of [3-(4-benzyloxy)phenoxy]benzo-[b]thiophene as an off-white solid. mp 84-86 C. 1 H NMR (CDCl3) delta 7.91-7.83 (m, 2H), 7.47-7.34 (m, 7H), 7.04 (q, JAB =9.0 Hz, 4H), 6.47 (s, 1H), 5.07 (s, 2H). Anal. Calcd. for C21 H16 O2 S: C, 75.88; H, 4.85. Found: C, 75.75; H, 5.00.
	In 2,3,5-trimethyl-pyridine;	Preparation 1 3-(4-Benzyloxyphenoxy)benzo[b]thiophene STR19 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2 was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3*150 mL). The organic was dried with sodium sulfate and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C). The remainder of the material was chromatographed (silicon dioxide, hexanes: ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of 3-(4-benzyloxyphenoxy)benzo[b]thiophene as an off-white solid.

	In 2,3,5-trimethyl-pyridine;	Preparation 1 3-(4-Benzyloxyphenoxy)benzo[b]thiophene To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, WI) to remove inorganic salts. The filtrate was washed with 1 N hydrochloric acid (3 x 150 mL). The organic was dried with sodium sulfate and concentrated in vacuoto a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C). The remainder of the material was chromatographed (silicon dioxide, hexanes: ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of 3-(4-benzyloxyphenoxy)benzo[b]thiophene as an off-white solid. mp 84-86 C. 1H-NMR (CDCI3) d 7.91-7.83 (m, 2H), 7.47-7.34 (m, 7H), 7.04 (q, JAB= 9.0 Hz, 4H), 6.47 (s, 1H), 5.07 (s, 2H).
	In 2,4,6-trimethyl-pyridine;	Preparation 1 3-(4-Benzyloxy)phenoxybenzo[b]thiophene To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous 2,4,6-collidine under N2is added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture is heated to reflux for 24 hours. Upon cooling, the reaction mixture is diluted with ethyl acetate (200 mL) and the crude mixture is filtered through a pad of Celite (Aldrich, Milwaukee, WI) to remove inorganic salts. The filtrate is washed with 1 N hydrochloric acid (3 x 150 mL). The organic is dried (sodium sulfate) and concentrated in vacuoto a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C). The remainder of the material is chromatographed (silicon dioxide, hexanes: ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of 3-(4-benzyloxy)phenoxybenzo[b]thiophene as an off-white solid. mp 84-86 C.

Reference： [1]Patent: US5985897,1999,A
[2]Patent: US5488058,1996,A
[3]Patent: US5843965,1998,A
[4]Patent: EP827959,1998,A2
[5]Patent: EP838462,1998,A1

41
[ 7342-82-7 ]
[ 103-16-2 ]
[ 1317-39-1 ]
[3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene[3-(4-benzyloxy)phenoxy]benzo [b]thiophene [ No CAS ]
[ 95-15-8 ]

Yield	Reaction Conditions	Operation in experiment
	In 2,3,5-trimethyl-pyridine;	Preparation 1 Preparation of [3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4-hydroxyphenyl)]benzo[b]thiophene[3-(4-benzyloxy)phenoxy]benzo [b]thiophene STR27 To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2 was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3 *150 mL). The organic was dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120 C.). The remainder of the material was chromatographed (silicon dioxide, hexanes: ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of [3-(4-benzyloxy)phenoxy]benzo-[b]thiophene as an off-white solid. mp 84-86 C. 1 H NMR (CDCl3) d 7.91-7.83 (m, 2H), 7.47-7.34 (m, 7H), 7.04 (q, JAB =9.0 Hz, 4H), 6.47 (s, 1H), 5.07 (s, 2H). Anal. calcd. for C21 H16 O2 S: C, 75.88; H, 4.85. Found: C, 75.75; H, 5.00.

Reference： [1]Patent: US5977093,1999,A

42
[ 103-16-2 ]
[ 107-07-3 ]
[ 67856-23-9 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 4h;	In contrast to the procedure reported by Xi et al. [13] , K2CO3 and DMF were used to prepare 1a instead of KOH and EtOH. To a mixture of 4-(benzyloxy)phenol (4.00 g, 20.0 mmol) and K2CO3 (4.15 g, 30.0 mmol) in anhydrous DMF (20 mL) was added 2-chloroethanol (2.01 g, 25.0 mmol) dropwise. The mixture was stirred at 90C for 4 h, and the solvent was removed by vacuum. A white precipitate was formed by adding 50 mL of 1 M NaOH, which was collected by filtration, washed with 50 mL of water and recrystallized from methanol to give 1a as a white solid (3.46 g,71%). m.p. 105.8-106.4 C. 1H NMR (400 MHz, CDCl3) d 7.46-7.30(m, 5H, Ph), 6.91 (d, J 9.1 Hz, 2H, Ph), 6.85 (d, J 9.0 Hz, 2H, Ph),5.02 (s, 2H, OCH2), 4.08-3.99 (m, 2H, CH2), 3.97-3.87 (m, 2H, CH2),1.95 (s, 1H, OH). MS (EI): m/z calcd for C15H16O3 244; found 244[M].
48.1%		11) Synthesis of 2-(4-(benzyloxy) phenoxy) ethanol (a compound 49a) The 4-benzyloxyphenol (4.00 g, 20.0 mmol) and KOH (1.12 g, 20.0 mmol) are dissolved in 30 ml of anhydrous ethanol, reflux is conducted for 30 min by heating at 80 C., 20 ml of 2-chloroethanol (2.01 g, 25 mmol) ethanol solution, continuously reaction is conducted for 1 h under a reflux and stirring state, reaction is monitored through TLC till basic completion, depressurization is conducted to remove solvent, 50 ml of 1M NaOH solution is added, white precipitate is separated out, suction filtration is conducted, the precipitate is washed with water and methanol recrystallization is conducted to obtain white crystal 49a (2.35 g, 48.1%). 1H NMR (400 MHz, CDCl3) delta 7.46-7.30 (m, 5H), 6.91 (d, J=9.1 Hz, 2H), 6.85 (d, J=9.0 Hz, 2H), 5.02 (s, 2H), 4.08-3.99 (m, 2H), 3.97-3.87 (m, 2H), 1.95 (s, 1H).
	With sodium hydroxide; In ethanol; dichloromethane;	Preparation 57 2-(4-Phenylmethoxy)phenoxy ethanol. A mixture of 130.4 g (0.65 mole) of 4-benzyloxyphenol (Eastman), 93.0 g (1.16 mole) of 2-chloroethanol (Aldrich) and 26.0 g (0.65 mole) of sodium hydroxide pellets in 750 ml of ethanol was stirred and heated at reflux for 20 hr. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to a solid residue. The solid was partitioned between 300 ml of 15% sodium hydroxide solution and 600 ml of methylene chloride. The organic layer was further washed with 200 ml of 15% sodium hydroxide solution, two 300 ml fractions of water, dried (magnesium sulfate) and the solvent was evaporated under reduced pressure to give 81.0 g of a solid. The solid was recrystallized (charcoal treated) from methylene chloride-petroleum ether (30-60 C.) to give 78.5 g (92%, based on amount of 4-benzyloxyphenol consumed) of crystals, mp 102.5-104.5 C. Analysis: Calculated for C15 H16 O3: C, 73.75; H, 6.60; Found: C, 73.73; H, 6.72.

Reference： [1]Chemistry Letters,2010,vol. 39,p. 415 - 417
[2]European Journal of Medicinal Chemistry,2015,vol. 104,p. 86 - 96
[3]Patent: US2017/37008,2017,A1 .Location in patent: Paragraph 0167
[4]Patent: US5194446,1993,A

43
[ 103-16-2 ]
[ 75390-09-9 ]
trans-4-[4-(phenylmethoxy)phenoxy]-1-phenylmethyl-3-pyrrolidinol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 32 Trans-4-[4-(phenylmethoxy)phenoxy]-1-phenylmethyl-3-pyrrolidinol A mixture of 40 g. of <strong>[75390-09-9]1-benzyl-3,4-epoxypyrrolidine</strong> and 42 g. of 4-benzoxyphenol was heated at 130 C. for 8 hr. On cooling, the mixture crystallized. Three crystallizations from petroleum ether-cyclohexane gave fluffy white crystals melting at 98.0-100.0 C. The yield was 6.0 g (8%). Analysis: Calculated for C24 H25 NO3: C,76.78; H,6.71; N,3.73. Found: C,76,83; H,6.82; N,3.57.
		EXAMPLE 32 Trans-4-[4-(phenylmethoxy)phenoxy]-1-phenylmethyl-3-pyrrolidinol A mixture of 40 g. of <strong>[75390-09-9]1-benzyl-3,4-epoxypyrrolidine</strong> and 42 g. of 4-benzoxyphenol was heated at 130 C. for 8 hr. On cooling, the mixture crystallized. Three crystallizations from petroleum ether-cyclohexane gave fluffy white crystals melting at 98.0-100.0 C. The yield was 6.0 g. (8%). Analysis: Calculated for C24 H25 NO3: C, 76.78; H, 6.71; N, 3.73. Found: C, 76.83; H, 6.82; N, 3.57.

Reference： [1]Patent: US4585785,1986,A
[2]Patent: US4452809,1984,A

44
[ 32601-86-8 ]
[ 103-16-2 ]
2-(4-benzyloxyphenoxy)-3-methylquinoxaline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide;	EXAMPLE 9 2-(4-Benzyloxyphenoxy)-3-methylquinoxaline In a nitrogen atmosphere, a solution of 28.0 g (0.14 mole) 4-benzyloxyphenol in 50 cc dimethylformamide was added dropwise at about 15 C. to 6.0 g (0.14 mole) 57% sodium hydride in 25 cc dimethylformamide. When the evolution of hydrogen ceased, 25.0 g (0.14 mole) <strong>[32601-86-8]<strong>[32601-86-8]2-chloro-3-methylquinoxalin</strong>e</strong> was added and the reaction mixture was heated at 125 C. for about 2 hours. After standing overnight at room temperature, the reaction mixture was poured into ice-water (~500 cc). The solid product was filtered and crystallized from methanol or acetonitrile to give 36.3 g of the title compound, m.p. 99-102 C. NMR (CDCl3)delta: 2.75 (s, 3H), 4.95 (s, 2H), 6.85-8.1 (m, 13H).

Reference： [1]Patent: US4609396,1986,A

45
[ 103-16-2 ]
[ 58841-52-4 ]
4-[(2-benzyloxyethoxy)phenyl]-benzyl ether [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	(b) 400 ml of ethanol and 15.8 g of 85% potasssium hydroxide are added to 40.0 g of hydroquinone monobenzyl ether and the mixture is heated to form a solution. Then 66 g of crude (2-benzyloxy)ethyl methanesulfonate are added to this solution and the reaction mixture is stirred for 24 hours under reflux. The precipitated salts are removed by filtration while still warm and 4-[(2-benzyloxyethoxy)phenyl]-benzyl ether is obtained from the cooled filtrate. Melting point: 72-73 C.

Reference： [1]Patent: US4727067,1988,A

46
[ 103-16-2 ]
3,4-dimethylphenyl(thioacetamide) [ No CAS ]
[ 23194-55-0 ]
[ 532-02-5 ]
[ 80-48-8 ]
N-(2-4'-benzyloxyphenoxypropyl)-3,4-dimethylphenylacetamidine naphthalene-2-sulphonate [ No CAS ]
[ 23194-54-9 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	EXAMPLE 96 By the methods of the relevant parts of Example I, 4-benzyloxyphenol was converted to 2-4'-benzyloxyphenoxypropionitrile, b.p. 166-172/0.7 mm., m.p. 84-86 (95% ethanol) and thence to 2-4'-benzyloxyphenoxypropylamine, b.p. 158-160/0.12 mm. The reaction between the amine (2.6 g.), 3,4-dimethylphenyl(thioacetamide) (1.8 g.) and methyl p-toluenesulphonate (1.9 g.) was carried out by the method of the second paragraph of Example III. The reaction mixture was treated with an excess of an aqueous solution of sodium naphthalene-2-sulphonate. The crystalline product was recrystallized from a mixture of ethanol and water and from a mixture of ethanol and ether to give N-(2-4'-benzyloxyphenoxypropyl)-3,4-dimethylphenylacetamidine naphthalene-2-sulphonate, m.p. 82-86.

Reference： [1]Patent: US3987158,1976,A

47
[ 103-16-2 ]
[ 588-09-0 ]
[ 865-33-8 ]
4-[4-(trifluoromethoxy)-2-nitrophenoxy]-phenyl benzyl ether [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; water; N,N-dimethyl-formamide;	EXAMPLE 3 2-[[4-[4-(trifluoromethoxy)-2-nitrophenoxy]phenoxy]]propanoic acid, methyl ester To a mixture of 10.01 g. of 4-(benzyloxy)phenol and 3.51 g. (0.05 mole) of potassium methoxide in 75 ml. of DMF is added 12.08 g. (0.05 mole) of <strong>[588-09-0]4-(trifluoromethoxy)-2-nitro-1-chlorobenzene</strong>. The mixture is heated to complete the reaction. Most of the solvent is removed at reduced pressure and the residue treated with methylene chloride and water. The methylene chloride solution is washed with saturated brine, dried, and the solvent removed, leaving 4-[4-(trifluoromethoxy)-2-nitrophenoxy]-phenyl benzyl ether.

Reference： [1]Patent: US4192669,1980,A

48
[ 4457-67-4 ]
[ 103-16-2 ]
[ 57725-41-4 ]

Yield	Reaction Conditions	Operation in experiment
	In acetone;	60°-61° is obtained in the usual manner (heating with acetone in the presence of excess potassium carbonate) from hydroquinone monobenzyl ether and (4-bromobutyl) methyl ether. Hydrogenation of this in methanolic solution (Raney nickel, 50 atmospheres gauge of H2, 50°) gives b 4-(4-methoxybutoxy)-phenol STR49 as an oil, boiling point 138°-143°/0.1 mm Hg.

Reference： [1]Patent: US4066768,1978,A

49
[ 192132-77-7 ]
[ 103-16-2 ]
[ 195516-73-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium <i>tert</i>-butylate In diethyl ether; N,N-dimethyl-formamide	15 Synthesis of 4-[2-(2-N-Boc-aminoethoxy)ethoxy]phenyl benzyl ether (15) EXAMPLE 15 Synthesis of 4-[2-(2-N-Boc-aminoethoxy)ethoxy]phenyl benzyl ether (15) In 30 ml of DMF, 2.0 g of p-benzyloxyphenol were dissolved, to which 1.2 g of t-BuOK were added. After the resulting mixture was stirred at room temperature for 30 minutes, 3.9 g of the compound (14) obtained in Example 14 were added. The mixture so obtained was stirred for 3 hours at room temperature. After the DMF was distilled off under reduced pressure, the residue was dissolved in ethyl ether. The resultant solution was washed once with dilute hydrochloric acid, twice with water, and once with a saturated aqueous solution H of sodium chloride. After the solution was dried over MgSO41 the ethyl ether was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column (eluent: CHCl3), whereby 3.2 g of the compound (15) were obtained (yield: 83%).

Reference： [1]Current Patent Assignee: SS Pharmaceutical Co., Ltd. - US6171520, 2001, B2

50
[ 110-87-2 ]
[ 103-16-2 ]
[ 53936-79-1 ]

Yield	Reaction Conditions	Operation in experiment
99%	With pyridinium p-toluenesulfonate; In dichloromethane; at 20℃; for 8h;Inert atmosphere; Cooling with ice;	To a 500-mi four-necked flask, 40.0 g (200 mmoi) of the compound (9-1), 1.0 g (4 mmol) of pyridinium p-toiuenesuifonate (PPTS), and 200 ml of dichioromethane were added in a nitrogen atmosphere, and the resulting mixture was stirred. While the mixture was cooled with ice, 25.2 g (300 mmol) of 3,4-dihydro-2H-pyran (DHP) was added dropwise to the mixture. Afier the mixture had been reacted at room temperature for 8 hours, the reaction liquid was cleaned with a saturated aqueous solution of sodium bicarbonate and a saturated saline solution in this ordet The organic layer was dried with sodium sulfate. After sodium sulfate had been removed by filtration, vacuum concentration was performed. Hereby, 56.3 g (yield: 99.0%) of the compound (9-2) was prepared
76%	With hydrogenchloride; at 20℃; for 4h;	Example 1; Step 1; To a stirred solution (without solvent) of 4-(benzyloxy)phenol (20 g, 0.1 mol) and 3,4-dihydropyran (23.5 g, 0.28 mol) was added concentrated hydrochloric acid (0.05 ml). The reaction mixture was stirred at 200C for 4 h. TLC Analysis showed only traces of starting material. A solution of 1 M NaOH (20 ml) was added to neutralize the mixture, keeping the temperature between 20 and 300C. The mixture was stirred for 10 min and isopropanol was added and again it was stirred for 10 min. Finally, the product was filtered and washed with water (2 x 22 ml). The solid was suspended in water (60 ml), isopropanol EPO <DP n="8"/>(25.5 ml) and 1 M NaOH (2.5 ml) and stirred for 15 min. The suspension was filtered and washed with water (10 ml). The solid product was dried in vacuum at 400C and gave 76% yield and 99.5% of HPLC purity (area).
6.7 g	With pyridinium p-toluenesulfonate; In dichloromethane; at 20℃; for 6h;Inert atmosphere; Cooling with ice;	Under a nitrogen atmosphere, 5.0 g of a compound represented by the formula (I-1-3) 0.2 g of pyridinium p-toluenesulfonate and 30 mL of dichloromethane were added. 2.3 g of 3,4-dihydro-2H-pyran was added dropwise while cooling with ice, and the mixture was stirred at room temperature for 6 hours. After washing with saturated aqueous sodium hydrogen carbonate solution and brine, Purification was carried out by column chromatography (alumina, dichloromethane) To obtain 6.7 g of a compound represented by the formula (I-1-4).

13.5 g	With pyridinium p-toluenesulfonate; In dichloromethane; at 20℃; for 7h;Cooling with ice;	10.0 g of the compound represented by Formula (I-11-10), 0.7 g of pyridinium p-toluenesulfonate, and 100 mL of dichloromethane were added to the reaction container. 4.6 g of 3,4-dihydro-2H-pyran was added dropwise thereto while cooling with ice, and the mixture was stirred at room temperature for 7 hours. After washing with a 5% sodium bicarbonate aqueous solution and a saline solution, purification was performed by column chromatography (alumina) to obtain 13.5 g of a compound represented by Formula (I-11-11).
13.5 g	With pyridinium p-toluenesulfonate; In dichloromethane; at 20℃; for 7h;Cooling with ice;	10.0 g of the compound represented by the formula (I-9-10), 0.7 g of p-toluenesulfonic acid pyridine cation, and 100 mL of dichloromethane were placed in a reaction vessel.While ice-cooling, 4.6 g of 3,4-dihydro-2H-pyran was added dropwise, and the mixture was stirred at room temperature for 7 hours.After washing with 5% aqueous sodium hydrogencarbonate solution and brine, by column chromatography (alumina, dichloromethane)Purification was carried out to obtain 13.5 g of the compound represented by the formula (I-9-11).
13.5 g	With pyridinium p-toluenesulfonate; In dichloromethane; at 20℃; for 7h;Cooling with ice;	Into a reactor, 10.0 g of a compound represented by formula (I-9-10), 0.7 g of pyridinium p-toluenesulfonate, and 100 mL of dichloromethane were added. While the mixture was being cooled over ice, 4.6 g of 3,4-dihydro-2H-pyran was added dropwise, followed by stirring at room temperature for 7 hours. After the mixture was washed with a 5% aqueous sodium hydrogen carbonate solution and brine, purification was performed by column chromatography (alumina, dichloromethane) so as to obtain 13.5 g of a compound represented by formula (I-9-9).

Reference： [1]Patent: US2017/260150,2017,A1 .Location in patent: Paragraph 0146; 0147
[2]Patent: WO2006/134124,2006,A1 .Location in patent: Page/Page column 6-7
[3]Patent: JP2018/35126,2018,A .Location in patent: Paragraph 0153; 0155
[4]Patent: US2018/354922,2018,A1 .Location in patent: Paragraph 0142; 0150
[5]Patent: TW2019/14995,2019,A .Location in patent: Paragraph 0150; 0152; 0160
[6]Patent: US2020/165215,2020,A1 .Location in patent: Paragraph 0130; 0138
[7]Patent: JP2020/93995,2020,A .Location in patent: Paragraph 0121-0122; 0126

51
[ 103-16-2 ]
[ 26487-67-2 ]
[ 1001470-41-2 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 4150 - 4169

52
[ 28868-76-0 ]
[ 103-16-2 ]
[ 1204483-46-4 ]

Yield	Reaction Conditions	Operation in experiment
29%	With caesium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 60 - 80℃; for 3.5h;	3b. Dimethyl 2-(4-benzyloxyphenoxy)malonate4-Benzyloxyphenol (1.0 g, 4.99 mmol), <strong>[28868-76-0]dimethyl 2-chloromalonate</strong> (998.2 mg, 5.99 mmol), cesium carbonate (3.25 g, 9.99 mmol) and potassium iodide (41.45 mg, 0.25 mmol) were stirred in 50 ml of DMF at 600C for 1.5 h. Addition of 200 mul of <strong>[28868-76-0]dimethyl 2-chloromalonate</strong> was followed by stirring at 600C for 1 h and at 800C for 1 h and concentration, and the residue was taken up in ethyl acetate and water. The organic phase was separated off, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 477 mg (29%), M+H+: 331.18.

Reference： [1]Patent: WO2010/3624,2010,A2 .Location in patent: Page/Page column 74
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 8679 - 8687

53
[ 103-16-2 ]
[ 5731-01-1 ]
C₂₇H₂₂O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 5872 - 5876

54
[ 103-16-2 ]
[ 96-99-1 ]
[ 943771-70-8 ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: 4-Benzyloxyphenol With potassium hydroxide In dimethyl sulfoxide at 20℃; for 0.166667h; Stage #2: 4-chloro-3-nitrobenzoate In dimethyl sulfoxide at 120℃; for 1h; Stage #3: With hydrogenchloride; water In dimethyl sulfoxide at 0℃;	43.43A Example 43; N-(2-Fluoro-phenyl)-4-(4-hydroxy-phenoxy)-3-(7-isopropyl^yrido[2,3-d]pyrimidin-4-ylamino)- benzamide; Example 43; A 4-(4-Benzyloxy-phenoxy)-3-nitro-benzoic acid; [0379] A solution of 4-Benzyloxy-phenol (2.00 g, 0.01 mol) and potassium hydroxide (1.12 g, 0.02 mol) in anhydrous dimethylsulfoxide (20 mL) was stirred at room temperature for 10 minutes under a nitrogen atmosphere. A solution of 4-chloro-3-nitrobenzoic acid (2.01 g, 0.01 mol) in dimethylsulfoxide (5 mL) was added and the mixture heated to 120° for 1 hour. The reaction was then cooled in an ice bath and poured into 100 mL of ice-water. The mixture was acidified with concentrated HCl to pH 3 then the resultant solid was colleted by vacuum filtration, washed with water and dried in a vacuum oven to provide the title product (3.5 g, 96%).

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2007/76034, 2007, A2 Location in patent: Page/Page column 102

55
[ 106-20-7 ]
[ 103-16-2 ]
[ 7693-46-1 ]
[ 1285718-51-5 ]

Yield	Reaction Conditions	Operation in experiment
27%	Stage #1: 4-Benzyloxyphenol; 4-Nitrophenyl chloroformate With triethylamine In dichloromethane at 20℃; for 48h; Inert atmosphere; Stage #2: 2-ethyl-N-(2-ethylhexyl)-1-hexanamine With triethylamine In dichloromethane at 20℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Misuraca, M. Cristina; Grecu, Tudor; Freixa, Zoraida; Garavini, Valentina; Hunter, Christopher A.; Van Leeuwen, Piet W.N.M.; Segarra-Maset, M. Dolores; Turega, Simon M. [Journal of Organic Chemistry, 2011, vol. 76, # 8, p. 2723 - 2732]

56
[ 103-16-2 ]
[ 118591-58-5 ]
[ 142879-00-3 ]

Reference： [1]Journal of Inclusion Phenomena and Macrocyclic Chemistry,2010,vol. 68,p. 261 - 270

57
[ 103-16-2 ]
[ 619-86-3 ]
4-(benzyloxy)phenyl 4-ethoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With dmap; dicyclohexyl-carbodiimide; In tetrahydrofuran; dichloromethane; at 20℃; for 12h;	2.9 g (18 mmol) of 4-ethoxybenzoicacid and 3.6 g (18 mmol) of 4-(benzyloxy)phenol were taken in a flask containing 60 mL of THF. To this stirred solution, dicyclohexylcarbodiimide (18 mmol) dissolved in 20 mL of THF was added followed by the addition of 4-dimethylaminopyridine (1.8 mmol) and stirring was continued at room temperature for overnight. Filtration of solid dicyclohexyl urea and subsequent evaporation of the solvent yielded a solid that was purified by recrystallization in isopropanal. The product was colorless crystalline solid. Yield: 73%. m.p.: 132-134. 1H NMR ppm (CDCl3): delta 8.13 (d, J = 7.5, 2H) 7.43 (t, J = 7.0, 2H) 7.40 (t, J = 7.0, 1H), 7.35 (d, J = 8.0, 2H), 7.09 (d, J = 8.0, 2H), 7.05 (d, J = 8.0, 2H), 6.19 (d, J = 8.0, 2H), 5.15 (s, 2H), 3.95 (q, J = 6.5, 2H), 0.97 (t, J = 6.0, 3H). 13C NMR ppm (CDCl3): delta 165.55, 163.20, 156.93, 144.30, 136.26, 132.35, 128.81, 128.37, 127.60, 122.54, 122.03, 115.15, 114.73, 70.25, 68.18, 13.96. IR (KBr, cm-1): 2934 and 2883 (-CH2str), 1719 (C=Ostr ester), 1605 and 1506 (C=Cstr aromatic), 1470 (-CHben), 1239 (C-O-Cstr of ester). EI-MS m/z: 348.3 (M+).

Reference： [1]Journal of Molecular Structure,2013,vol. 1038,p. 126 - 133

58
[ 19578-68-8 ]
[ 103-16-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With glycolic Acid; copper hydroxide; sodium hydroxide In water; dimethyl sulfoxide at 120℃; for 6h; Inert atmosphere; Schlenk technique;
76%	With copper(I) oxide; 2-(N,N-dimethylamino)ethanol; water; potassium hydroxide In dimethyl sulfoxide at 100℃; for 24h; Inert atmosphere;	General Procedure B. General procedure: To a test tube containing a magnetic bar was added aryl halide (1.0 mmol), Cu2O (14.3 mg, 0.1 mmol), KOH (169 mg, 3.0 mmol), 2-dimethylaminoethanol (0.3 mL, 3.0 mmol), and DMSO/H2O (1.5 mL/0.5 mL). After flushing with argon, the mixture was stirred in a preheated oil bath at 100 °C for 24 h. After cooled to ambient temperature, the reaction mixture was distributed in aqueous HCl (5 %) and ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous MgSO4, and concentrated under vacuum. The crude product was further purified by column chromatography (EtOAc/n-Hexane) to provide the phenols.

Reference： [1]Xiao, Yan; Xu, Yongnan; Cheon, Hwan-Sung; Chae, Junghyun [Journal of Organic Chemistry, 2013, vol. 78, # 11, p. 5804 - 5809]
[2]Kim, Jihye; Battsengel, Oyunsaikhan; Liu, Yajun; Chae, Junghyun [Bulletin of the Korean Chemical Society, 2015, vol. 36, # 12, p. 2833 - 2840]

59
[ 103-16-2 ]
[ 169457-73-2 ]
[ 158550-61-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium carbonate; potassium iodide; In acetone; at 0 - 30℃;Inert atmosphere; Reflux;	tert-Butyl 4-[2-[4-(Benzyloxy)phenoxy]ethyl]piperidine-1-carboxylate Into a 100-mL round-bottom flask was placed a solution of 2-[1-(tert-butoxycarbonyl)-4-piperidinyl]ethanol (1.10 g, 4.80 mmol) and tetrabromomethane (2.40 g, 7.24 mmol, 1.86 equiv.) in tetrahydrofuran (30 mL). Triphenylphosphine (1.26 g, 4.80 mmol, 1.00 equiv.) in CH2Cl2 was added slowly under N2 at 0 C. The resulting solution was stirred overnight at 30 C. and then concentrated under vacuum. The residue was applied onto a silica gel column, which was eluted with EtOAc/petroleum ether 1:10 to 1:5. This resulted in 1.22 g (87%) of the bromide as a colorless oil. A solution/suspension of <strong>[169457-73-2]tert-butyl 4-(2-bromoethyl)piperidine-1-carboxylate</strong> (1.22 g, 4.18 mmol), 4-(benzyloxy)phenol (1.01 g, 5.04 mmol, 1.20 equiv.), K2CO3 (830 mg, 6.01 mmol, 1.40 equiv.) and KI (75 mg, 0.45 mmol, 0.11 equiv.) in acetone was heated to reflux under N2 overnight. After cooling to room temperature, the mixture was diluted with 100 mL of EtOAc, and the solids were filtered off. The filtrate was concentrated under vacuum, and the residue was applied onto a silica gel column, which was eluted with ethyl acetate/petroleum ether (1:5) to afford the product (1.25 g, 73%) as a white solid. 1H NMR (CDCl3, 300 MHz) delta 7.43-7.29 (m, 5H), 6.90 (d, 2H, J=6.6 Hz), 5.01 (s, 2H), 4.08 (d, 2H, J=7.2 Hz), 3.95 (t, 1H, J=4.2 Hz), 2.70 (t, 2H, J=9.6 Hz), 1.71-1.69 (m, 5H), 1.45 (s, 9H), 1.20-1.15 (m, 2H). LC-MS (ESI) m/z 434 (M+Na+).

Reference： [1]Patent: US2013/184313,2013,A1 .Location in patent: Paragraph 1667

60
[ 10320-42-0 ]
[ 103-16-2 ]
2-(4-benzyloxyphenoxy)-5-nitropyrimidine [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 937 - 941

61
[ 103-16-2 ]
[ 2695-48-9 ]
1-(benzyloxy)-4-(oct-7-en-1-yloxy)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With potassium carbonate; In N,N-dimethyl-formamide; at 65℃; for 48h;	A mixture of 8-bromooct-1-ene (4.3 g; 22 mmol), 4-benzyloxyphenol (24, 4.0 g; 20 mmol), potassium carbonate (5.8 g; 40 mmol) and DMF (50 mL) was stirred and heated at 65 C for 48 h. After cooling to room temperature, the mixture was diluted with water (200 mL) and extracted with toluene (4 × 60 mL). The combined organic solution was washed with water (50 mL), brine (50 mL) and dried with anhydrous magnesium sulfate. The crude product after evaporation was purified by column chromatography (toluene) to yield 6.0 g (97%) of ether 23, m.p. 64-65 C. 1H NMR: 1.30-1.45 (m, 6 H, (CH2)3), 1.76 (m, 2 H, CH2CH2O), 2.06 (m, 2 H, CH2CH=CH2), 3.90 (t, 2 H, J = 6.5, CH2O), 4.97 (m, 4 H, CH2O, CH=CH2), 5.79 (m, 1 H, CH=CH2), 6.82 (d, 2 H, J = 9.1), 6.90 (d, 2 H, J = 9.1), 7.38 (m, 5 H). Elemental analysis: for C21H26O2 (310.43): calculated C 81.25, H 8.44; found C 81.44, H 8.39%.

Reference： [1]Beilstein Journal of Organic Chemistry,2014,vol. 10,p. 794 - 807

62
[ 103-16-2 ]
[ 122-94-1 ]

Reference： [1]Molecular Crystals and Liquid Crystals,2013,vol. 570,p. 20 - 35
[2]RSC Advances,2015,vol. 5,p. 105066 - 105078

63
[ 103-16-2 ]
[ 35103-79-8 ]
p-(benzyloxy)calix[7]arene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; water;	Example A.1 Concentration of Caesium Hydroxide of 0.15 Equivalent A suspension of 50.6 g of p-(benzyloxy)phenol (0.254 mol), 20 g (0.667 mol) of paraformaldehyde (melting point: 135 C.) in 700 ml of xylene is placed under argon in a 2-litre three-necked flask equipped with a mechanical stirrer and a "Dean-Stark" type water trap. The suspension heated with stirring. When the temperature reaches 90 C., 7.4 ml (0.0425 mol) of a solution of CsOH at 50% (by weight) in water is added rapidly using a syringe (and under flushing with argon). The suspension is left under reflux for 6 h, during which period of time the formation of a voluminous white precipitate is observed. This precipitate is filtered, washed with xylene, then with pentane. M=35 g, yield of p-(benzyloxy)calix[7]arene (in the form of caesium monosalt): 58% The spectroscopic characteristics of this precipitate correspond to that of a monoanion of p-(benzyloxy)calix[7]arene. 1H NMR (DMSO-d6): (chemical shifts, ppm) 7.60-7.20 (multiplet, aromatics); 6.72 (fine singlet, hydroquinone); 4.93 (fine singlet, benzyl protons); 3.71 (fine singlet, intracyclic methylenes). Mass spectrometry (MALDI, DHB matrix): m/z=1617.41 (M+Cs)+.

Reference： [1]Patent: US2015/232603,2015,A1

64
[ 103-16-2 ]
[ 35103-79-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; caesium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; [(2)H6]acetone; water; dimethyl sulfoxide;	Example A.2 Concentration of Caesium Hydroxide of 0.3 Equivalent A suspension of 50.6 g of p-(benzyloxy)phenol (0.254 mol), 20 g (0.667 mol) of paraformaldehyde (melting point: 135 C.) in 700 ml of xylene is placed under argon in a 2-litre three-necked flask equipped with a mechanical stirrer and a "Dean-Stark" type water trap. The suspension is heated with stirring. When the temperature reaches 90 C., 14.8 ml (0.085 mol) of a solution of CsOH at 50% (by weight) in water is added rapidly using a syringe (and under flushing with argon). The suspension is left under reflux for 5 h 30. Then a perfectly clear bright orange solution is obtained. 100 ml of a solution of 37% HCl in water is then added, and the formation of a precipitate is observed. The suspension is left under vigorous stirring for two days, then evaporated to dryness in a rotavapor. After washing with 500 ml of water (removal of the salts and excess HCl), the solid is dissolved hot (130 C.) in 200 ml of DMSO. Then a clear solution black is obtained, to which 2 l of acetone is added hot. After returning to ambient temperature, this clear solution is left for a week, during which a crystalline precipitate of p-(benzyloxy)calix[6]arene (18 g) is deposited on the walls of flask. The filtrate is evaporated in a rotary evaporator, then with a heat gun until a black solid is obtained. This solid is washed with acetone, which leads to the recovery of a second batch of p-(benzyloxy)calix[6]arene (10 g). Total: 28 g, yield 51%.

Reference： [1]Patent: US2015/232603,2015,A1

65
[ 103-16-2 ]
[ 1498-51-7 ]
bis(4-(benzyloxy)phenyl) ethyl phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydride; In tetrahydrofuran;Reflux;	To a solution of 4-benzyloxyphenol (10.0 g, 50 mmol) in THF (200 mL) was added 95% NaH (1.26 g, 50 mmol). After the reaction was complete, ethyl dichlorophosphate (3.0 mL, 25 mmol) was added dropwise. The mixture was refluxed overnight then cooled to ambient temperature. 100 mL water was then added. The layers were separated and the aqueous layer was extracted with ether (200 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to give 11.20 g (91%) of a brown oil.

Reference： [1]RSC Advances,2015,vol. 5,p. 74712 - 74719
[2]Patent: US10155906,2018,B1 .Location in patent: Page/Page column 5; 6

66
[ 32315-10-9 ]
[ 103-16-2 ]
[ 52177-75-0 ]

Yield	Reaction Conditions	Operation in experiment
> 99%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0℃; for 16h;	Preparation Example 2-1: 4-(Benzyloxy)phenyl chloroformate (III-1) Triphosgene (2.37 g, 7.99 mmol, 0.8 eq) was dissolved in anhydrous THF solvent at anhydrous condition. To the resulting solution was added 4-(benzyloxy)phenol (2.00 g, 9.99 mmol, 1.0 eq) dissolved in anhydrous THF solvent. To the resulting mixture was slowly added diisopropylethylamine (DIPEA) (1.74 ml, 9.99 mmol, 1.0 eq) and the resulting mixture was stirred at 0 C for 16 hrs. And then, the mixture was extracted with ethyl acetate and distilled water, and the distilled water was removed from the resulting ethyl acetate solution using anhydrous magnesium sulfate. The ethylacetate solvent was removed using a rotary evaporator to give the title compound as a white solid (III-1) (2.667 g, 10.15mmol, >99 %). 1H-NMR (400 MHz, CDCl3) delta: 7.46-7.34 (5 H, m), 7.18-7.13 (2 H, m), 7.02-6.68 (2 H, m).
> 99%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 20℃; for 1h;	To a solution of 4-(benzyloxy)phenol (3, 0.50 g,2.49 mmol) and triphosgene (0.37 g, 1.24 mmol) in THF(10 mL), DIPEA (0.57 mL, 3.24 mmol) was added dropwiseat 0 C. The resulting solution was allowed to warmto room temperature and stirred for 1 h. After the reactionwas complete (TLC), the resulting mixture was concentratedunder reduced pressure, treated with water andextracted with dichloromethane (2x). The combined organiclayer was dried over with anhydrous MgSO4 and filtered.Removal of the solvent afforded the desired product 4 as awhite solid, which was used for the next step without anypurification: mp 83.6-87.3 C; 1H NMR (400 MHz,CDCl3) delta 7.46-7.35 (5H, m), 7.16 (2H, dt, J = 9.2 and2.9 Hz), 7.01 (2H, dt, J = 8.8 and 2.8 Hz), 5.08 (2H, s);13C NMR (100 MHz, CDCl3) delta 157.3, 150.0, 145.4, 136.4,128.7, 128.2, 127.5, 121.4, 115.6, 70.5; MS: not detected.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 94 - 99
[2]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5193 - 5197
[3]Patent: EP3269709,2018,A1 .Location in patent: Paragraph 0060-0061
[4]Bulletin of the Korean Chemical Society,2018,vol. 39,p. 891 - 894

67
[ 103-16-2 ]
[ 16024-60-5 ]
C₂₂H₂₈O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 4-Benzyloxyphenol; 3,6,9,12-tetraoxatridecanoic acid With dmap In tetrahydrofuran at 0℃; for 0.5h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 0 - 20℃;	2,5,8,11-Tetraoxatridecanoic acid, 1-[4-(phenylmethoxy)phenoxy] ester (2d) To a solution of compound 2c (200 mg, 0.9 mmol) and 4-benzyloxylphenol (270 mg, 1.35 mmol) were dissolved in THF (15 mL). 4-(Dimethylamino)pyridine (7 mg, 6.3 mol %) was added to reaction mixture. After stirring for 30 min at 0 °C, EDC×HCl (189 mg, 0.99 mmol) was added to the reaction mixture and then stirred for 1h. The reaction mixture was warmed and stirred overnight at room temperature. The reaction mixture was filtered and then filtrate was evaporated in vacuo. Dichloromethane (10 mL) was added and the filtration was repeated one more. The filtrate was evaporated and the residue was purified using silica gel flash chromatography (hexane/ethyl acetate/MeOH =100/100/0 to 100/100/2) to give the desire product 2d (250 mg, 0.62 mmol, yield: 69 %) as a viscous liquid.

Reference： [1]Le, Hoa Thi; Hong, Bin Na; Lee, Yeong Ro; Cheon, Ji Hyun; Kang, Tong Ho; Kim, Tae Woo [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 2, p. 699 - 705]

68
[ 455-88-9 ]
[ 103-16-2 ]
4-(4-benzyloxyphenoxy)-3-methylnitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%		An aqueous solution of 5M sodium hydroxide (2.0 ml, 10 mmol)was added to DMSO (8 ml) at room temperature under an Ar atmosphere.After 10 min, O-monobenzylhydroquinone (961 mg, 4.8 mmol)was added to it. The mixture was stirred at 50 °C for 15 min, then <strong>[455-88-9]2-fluoro-5-nitrotoluene</strong> (620 mg, 4.0 mmol) was added, and stirring wascontinued at 50 °C for 5.5 h, and at room temperature for 15 h. Thereaction mixture was then poured into ice water and the precipitate was collected by filtration to give 29a (R2=2-Me, 1.04 g, 65percent).29a (R2=2-Me): Yellow powder; 1H NMR (600 MHz, CDCl3) delta 8.13(d, J=2.1 Hz, 1H), 7.96 (dd, J=8.9, 2.7 Hz, 1H), 7.36 (m, 5H), 7.02(dt, J=9.6, 2.8 Hz, 2H), 6.99 (dt, J=8.9, 2.7 Hz, 2H), 6.69 (d,J=8.9 Hz, 1H), 5.08 (s, 2H), 2.42 (s, 3H); 13C NMR (150 MHz, CDCl3)delta 162.21, 156.04, 148.51, 142.06, 136.67, 128.65, 128.12, 127.48,126.64, 123.14, 121.50, 116.24, 114.47.

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 1028 - 1033
[2]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 5118 - 5127

69
[ 6320-15-6 ]
[ 103-16-2 ]
4-(4-(benzyloxy)phenoxy)-2,6-dimethoxypyrimidine [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 3850 - 3853

70
[ 103-16-2 ]
[ 568-72-9 ]
9-(4-(benzyloxy)phenoxy)-1,6,6-trimethyl-6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In chlorobenzene at 120℃; for 36h; Sealed tube; regioselective reaction;	Typical experimental procedure for the catalyst-free Aromatic ethers reaction. General procedure: A 10 mL sealed tube was charged with Tan-IIA substrates (0.1 mmol), various phenol (0.17 mmol), and TEMPO (0.2 mmol). PhCl (1 mL) was added, and the resulting mixture was stirred at 120°C. The reaction was monitored by TLC until the starting material disappeared. Then the solvent was removed under vacuum, and the resulting residue was purified by chromatography on a silica gel column to furnish the desired compound 4 as red solids.

Reference： [1]Liang, Bing; Yu, Shujuan; Li, Jie; Wang, Fan; Liang, Gaolin; Zhang, Ao; Ding, Chunyong [Tetrahedron Letters, 2017, vol. 58, # 19, p. 1822 - 1825]

71
[ 103-16-2 ]
[ 946-80-5 ]

Yield	Reaction Conditions	Operation in experiment
88%		Benzyloxyphenol (20 mmol, 4 g) was dissolved in dimethyl sulfoxide,Et3N (1.2 eq) was added, a saline plug was placed, a balloon filled with sulfuryl fluoride gas was inserted,The reaction was monitored by TLC plate, sulfuryl fluoride balloon was completely removed after the conversion of raw materials,To the reaction solution were further added Pd (OAc) 2 (2 mol%), dppp (2.4 mol%),Et3N (4eq), HCOOH (4eq), the reaction was continued at room temperature, TCL plate detection,When the reaction is complete, quench with water, extract with dichloromethane three times, combine the organic phases,Washed three times with water, dried over anhydrous sodium sulfate, the dichloromethane was removed in vacuo at low temperature,Separation with silica gel column to give a white solid 3.2g, isolated 88% yield.
78%		General procedure: A mixture of 1 (1.0 mmol), Et3N (1.2 eq, 3.0 mmol, 120.4 mg), and DMSO (3 mL) was allowed to stir at room temperature under the atmosphere of a SO2F2 balloon for 3 to 6 hours (until the complete consumption of phenol starting materials), before a mixture of Pd(OAc)2 (2 mol%, 4.04 mg), dppp (2.4 mol%, 10.1 mg), Et3N (4 eq, 4.0 mmol, 400.4 mg), and HCOOH (4 eq, 4.0 mmol, 182.2 mg) were added into the reaction mixture and allowed to react for an additional 2-4 hours at room temperature (monitored by TLC until the complete consumption fluorosulfates intermediates ). The reaction mixture was extracted with dichloromethane (3 × 20 mL) and the extracts were washed with water, dried over anhydrous Na2SO4, and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel using hexanes as eluents to give the desired product (3).

Reference： [1]Patent: CN107286061,2017,A .Location in patent: Paragraph 0032; 0033; 0034
[2]Tetrahedron Letters,2017,vol. 58,p. 2340 - 2343

72
[ 103-16-2 ]
[ 352432-46-3 ]
[ 497-76-7 ]

Yield	Reaction Conditions	Operation in experiment
	With quinoline; In toluene; at 80℃; for 10h;Inert atmosphere; Molecular sieve;	4 g of 4-benzyloxyphenol and 4 ml of quinoline were added to 100 ml of toluene and stirred and dissolved, and then 5 g 4A molecular sieves. Then, in an argon atmosphere, 11.5 g of 2,3,4,6-tetra-O-trimethylsilyl-1-iodo-a-D-glucose In toluene was added to the reaction solution and reacted at 80 C for 10 hours. After completion of the reaction, the mixture was filtered, washed with water and the solvent was dried The solution was dissolved in methanol, palladium on carbon was added, reacted in a hydrogen atmosphere for 2 hours, palladium on carbon was filtered, acetic acid was added to the solution, The mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was concentrated and acetone was added to give a white solid which was filtered, washed with acetone The filter cake was dissolved in a mixed solvent of water and acetone, and the mixture was filtered and dried to obtain a white arbutin solid.

Reference： [1]Patent: CN103923133,2016,B .Location in patent: Paragraph 0032-0033

73
[ 103-16-2 ]
[ 53936-56-4 ]

Reference： [1]Patent: US2017/260150,2017,A1
[2]Patent: JP2018/35126,2018,A
[3]Patent: US2018/354922,2018,A1
[4]Patent: TW2019/14995,2019,A

74
[ 103-16-2 ]
[ 41317-15-1 ]
C₂₇H₂₅NO₃ [ No CAS ]

Reference： [1]ACS Catalysis,2017,vol. 7,p. 2446 - 2451

75
[ 103-16-2 ]
[ 64-19-7 ]
[ 30992-63-3 ]

Reference： [1]RSC Advances,2018,vol. 8,p. 7716 - 7725

76
[ 208167-83-3 ]
[ 103-16-2 ]
tert-butyl 4-[2-(4-benzyloxyphenoxy)ethyl]piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With caesium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 80℃; for 10h;Inert atmosphere;	To a solution of tert-butyl 4-(2-chloroethyl)piperazine- l-carboxylate (1.00 g, 4.02 mmol, 1.00 eq), 4-benzyloxyphenol (965 mg, 4.82 mmol, 1.20 eq) in N,N-dimethylformamide (20 mL) was added cesium carbonate (1.57 g, 4.82 mmol, 1.20 eq) and potassium iodide (66 mg, 0.4 mmol, 0.10 eq) under nitrogen. The reaction was stirred at 80 C for 10 hours. TLC (Petroleum ether/Ethyl acetate = 3/1) and LC/MS showed most of the starting material was consumed. Water (100 mL) was added to the mixture, and the resulting mixture was extracted with ethyl acetate (50 mL x 3). The combined organic phase was washed with brine (80 mL), dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1 to 3/1) to provide tert- butyl 4-[2-(4-benzyloxyphenoxy)ethyl]piperazine-l-carboxylate (1.4 g, 3.39 mmol, 84% yield) as a colorless oil. 1H NMR (400MHz, CDC13) delta 7.46 - 7.29 (m, 5H), 6.95 - 6.88 (m, 2H), 6.88 - 6.81 (m, 2H), 5.02 (s, 2H), 4.07 (t, = 5.8 Hz, 2H), 3.51 - 3.42 (m, 4H), 2.80 (t, = 5.8 Hz, 2H), 2.56 - 2.48 (m, 4H), 1.47 (s, 9H).
84%	With caesium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 80℃; for 10h;Inert atmosphere;	To a solution of <strong>[208167-83-3]ter<strong>[208167-83-3]t-butyl 4-(2-chloroethyl)piperazine-1-carboxylate</strong></strong> (1.00 g, 4.02 mmol, 1.00 eq), 4-benzyloxyphenol (965 mg, 4.82 mmol, 1.20 eq) in N,N-dimethylformamide (20 mL) was added cesium carbonate (1.57 g, 4.82 mmol, 1.20 eq) and potassium iodide (66 mg, 0.4 mmol, 0.10 eq) under nitrogen. The reaction was stirred at 80 C. for 10 hours. TLC (Petroleum ether/Ethyl acetate=3/1) and LCMS showed most of the starting material was consumed. Water (100 mL) was added to the mixture, the resulting mixture was extracted with Ethyl acetate (50 mL*3). The combined organic phase was washed with brine (80 mL), dried over sodium sulfate, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (Petroleum ether/Ethyl acetate=50/1 to 3/1). tert-butyl 4-[2-(4-benzyloxyphenoxy)ethyl]piperazine-1-carboxylate (1.4 g, 3.39 mmol, 84% yield) was obtained as a colorless oil. Chemical Formula: C24H32N2O4, Molecular Weight: 412.5 Total H count from HNMR data: 32. ?H NMR: (400 MHz, CHEOROFORM-d)oe: 7.46-7.29 (m, 5H), 6.95-6.88 (m, 2H), 6.88-6.812H), 5.02 (s, 2H), 4.07 (t, J=5.8 Hz, 2H), 3.5 1-3.42 (m, 4H), 2.80 (t, J=5.8 Hz, 2H), 2.56-2.48 (m, 4H), 1.47 (s, 9H)

Reference： [1]Patent: WO2018/140809,2018,A1 .Location in patent: Paragraph 00402; 00671; 00672; 00673
[2]Patent: US2018/215731,2018,A1 .Location in patent: Paragraph 1264; 1266; 1267; 1268; 1269; 1270; 1271

77
[ 402-67-5 ]
[ 103-16-2 ]
C₁₉H₁₅NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate In N,N-dimethyl-formamide at 80 - 150℃; for 27h;	A mixture of p-(benzyloxy)phenol (220 mg, 1.10 mmol), m-fluoronitrobenzene(149 mg, 1.05 mmol), and potassium carbonate (173 mg,1.25 mmol) in DMF (1.5 ml) was stirred at 150 °C for 3 h, and at 80 °Cfor 24 h. It was allowed to cool to room temperature, then 1M HCl wasadded, and the mixture was extracted with ethyl acetate. The organiclayer was dried over sodium sulfate, and evaporated. The residue waspurified by silica gel column chromatography (hexane/ethyl acetate19:1) to afford 22a (237 mg, 70%)22a: 1H NMR (600 MHz, CDCl3) δ 7.89 (ddd, J=7.8, 2.4, 0.6 Hz,1H), 7.72 (t, J=2.4 Hz, 1H), 7.43 (m, 5H), 7.35 (t, J=5.4 Hz, 1H),7.28 (ddd, J=8.4, 2.4, 0.6 Hz, 1H), 7.01 (s, 4H), 5.08 (s, 2H).

Reference： [1]Kazui, Yuko; Fujii, Shinya; Yamada, Ayumi; Ishigami-Yuasa, Mari; Kagechika, Hiroyuki; Tanatani, Aya [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 18, p. 5118 - 5127]

78
[ 446-10-6 ]
[ 103-16-2 ]
C₂₀H₁₇NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 80 - 150℃; for 27h;	General procedure: A mixture of p-(benzyloxy)phenol (220 mg, 1.10 mmol), m-fluoronitrobenzene(149 mg, 1.05 mmol), and potassium carbonate (173 mg,1.25 mmol) in DMF (1.5 ml) was stirred at 150 C for 3 h, and at 80 Cfor 24 h. It was allowed to cool to room temperature, then 1M HCl wasadded, and the mixture was extracted with ethyl acetate. The organiclayer was dried over sodium sulfate, and evaporated. The residue waspurified by silica gel column chromatography (hexane/ethyl acetate19:1) to afford 22a (237 mg, 70%)

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 5118 - 5127

79
[ 103-16-2 ]
[ 769-10-8 ]
C₂₀H₁₇NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 80 - 150℃; for 27h;	General procedure: A mixture of p-(benzyloxy)phenol (220 mg, 1.10 mmol), m-fluoronitrobenzene(149 mg, 1.05 mmol), and potassium carbonate (173 mg,1.25 mmol) in DMF (1.5 ml) was stirred at 150 C for 3 h, and at 80 Cfor 24 h. It was allowed to cool to room temperature, then 1M HCl wasadded, and the mixture was extracted with ethyl acetate. The organiclayer was dried over sodium sulfate, and evaporated. The residue waspurified by silica gel column chromatography (hexane/ethyl acetate19:1) to afford 22a (237 mg, 70%)

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 5118 - 5127

80
[ 103-16-2 ]
[ 1427-07-2 ]
C₂₀H₁₇NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 80 - 150℃; for 27h;	General procedure: A mixture of p-(benzyloxy)phenol (220 mg, 1.10 mmol), m-fluoronitrobenzene(149 mg, 1.05 mmol), and potassium carbonate (173 mg,1.25 mmol) in DMF (1.5 ml) was stirred at 150 C for 3 h, and at 80 Cfor 24 h. It was allowed to cool to room temperature, then 1M HCl wasadded, and the mixture was extracted with ethyl acetate. The organiclayer was dried over sodium sulfate, and evaporated. The residue waspurified by silica gel column chromatography (hexane/ethyl acetate19:1) to afford 22a (237 mg, 70%)

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 5118 - 5127

81
[ 103-16-2 ]
[ 37002-45-2 ]
(5-(4-(benzyloxy)phenoxy)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate [ No CAS ]

Reference： [1]Molecular Pharmaceutics,2018,vol. 15,p. 5574 - 5584

82
[ 103-16-2 ]
[ 556-48-9 ]
[ 108-88-3 ]

Yield	Reaction Conditions	Operation in experiment
1: 99% 2: 99%	With hydrogen In n-heptane at 140℃; for 6h;

Reference： [1]Song, Yang; Li, Zhe; Ji, Pengfei; Kaufmann, Michael; Feng, Xuanyu; Chen, Justin S.; Wang, Cheng; Lin, Wenbin [ACS Catalysis, 2019, vol. 9, # 2, p. 1578 - 1583]

83
[ 103-16-2 ]
[ 87789-47-7 ]

Reference： [1]Patent: WO2019/139714,2019,A1

84
[ 103-16-2 ]
[ 1064194-10-0 ]
tert-butyl 3-(4-(benzyloxy)phenoxy)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2019/157020,2019,A1 .Location in patent: Paragraph 0312; 0322

85
[ 1140923-83-6 ]
[ 103-16-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With [2,2]bipyridinyl; (1,2-dimethoxyethane)dichloronickel(II); water; bis(pinacol)diborane; lithium tert-butoxide; In methanol; N,N-dimethyl acetamide; at 30℃; for 24h;Schlenk technique;	Take a 10ml dry Schlenk reaction tube.In this order, for example, 0.3 mmol of B2Pin20.01 mmol NiCl 2 (DME),0.02 mmol organic ligand L4,0.2 mmol of the starting material (I) and 0.4 mmol of lithium t-butoxide were operated in a double-row tube three times;Inject DMA2ml in sequence, water 50ul, 0.1mmol methanol;It was then vigorously stirred at 30 C for 24 h.After the reaction was completed, the pH was adjusted to 2 by adding 1 M hydrochloric acid, and then 20 ml of water was added thereto, and extracted with 20 ml of ethyl acetate, and the organic phase was collected and washed with saturated brine.It is dried over anhydrous magnesium sulfate, concentrated, and then separated with a 200 mesh silica gel column.Thus, the product (II) was obtained in a yield of 91%.
91%	With 6,6'-dimethyl-2,2'-bipyridine; (1,2-dimethoxyethane)dichloronickel(II); bis(pinacol)diborane; lithium tert-butoxide; In methanol; N,N-dimethyl acetamide; water; at 30℃; for 24h;Inert atmosphere; Glovebox; Sealed tube;	General procedure: In glovebox, B2pin2 (76.17 mg, 0.3 mmol, 1.5 equiv), NiCl2(DME) (2.20 mg, 0.01 mmol, 0.05 equiv),6,6-dimethyl-2,2-dipyridyl (3.68 mg, 0.02 mmol, 0.10 equiv), LiOtBu (32 mg, 0.4 mmol, 2.0 equiv), and protected phenol (if solid) (0.2 mmol) were added to an oven-dried tube. The reaction tube wasequipped with a magnetic stir bar and sealed with Teflon-lined cap, refilled the system with argonand performed two more evacuation-backfill cycles, protected phenol was added by syringe underargon flow (if liquid). DMA (2.00 mL), H2O (50 muL), MeOH (25 muL) were added to the tubesequentially. The reaction mixture turned dark and was stirred at 30 C for 24 h. When the reactionwas finished, 10 mL aqueous HCl (0.1 M) was added to the mixture and extracted with CH2Cl2 (2 ×10 mL), dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purifiedby silica gel flash chromatography to give the product.

Reference： [1]Patent: CN110256205,2019,A .Location in patent: Paragraph 0204-0208
[2]Molecules,2020,vol. 25

86
[ 103-16-2 ]
[ 31480-93-0 ]

Reference： [1]Patent: JP2020/93995,2020,A

87
[ 6373-46-2 ]
[ 103-16-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With uranyl nitrate hydrate; water; trifluoroacetic acid In acetonitrile for 48h; Irradiation; Inert atmosphere;	31 Example 31 In a 25mL reaction tube, add 4-benzyloxyaniline (0.2mmol, 39.8mg), water (0.6mmol, 10.8mg), uranyl nitrate hydrate (4mol%/0.008mmol, 4.0mg),Trifluoroacetic acid (0.2mmol, 22.8mg), acetonitrile (2mL), Stir under the irradiation of a 6-watt blue LED lamp (wavelength: 460nm) in a nitrogen atmosphere for 2 days. After the reaction is complete, extract, concentrate, and separate by column chromatography (VPE/VEA=10/1) to obtain a white solid 3ae (34.0mg, 85 %).

Reference： [1]Current Patent Assignee: EAST CHINA NORMAL UNIVERSITY - CN112778125, 2021, A Location in patent: Paragraph 0162-0165

88
[ 946-80-5 ]
[ 103-16-2 ]

Yield	Reaction Conditions	Operation in experiment
80%	With dirhodium tetraacetate; [bis(acetoxy)iodo]benzene; trifluoroacetic anhydride at 80℃; for 1.5h;	1 Example 1 Add compound 1a (9mmol), rhodium acetate dimer (0.135mmol) and iodobenzene diethylester (9mmol) into a 75mL pressure tube, then add trifluoroacetic anhydride (30mL), and place it in an oil bath at 80°C. The reaction was stirred at medium magnetic force for 1.5 hours. After the reaction was completed, the reaction solution was transferred to a round bottom flask, and trifluoroacetic anhydride was distilled off at 70°C, and then extracted with ethyl acetate (60 mL×3), the organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate , Remove the solvent by distillation under reduced pressure, and separate by column chromatography (petroleum ether:Ethyl acetate = 8:1, v/v) to obtain a white solid product 2a,The yield is 80%.
65%	With [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂; trifluoroacetic anhydride; bis-[(trifluoroacetoxy)iodo]benzene at 80℃; for 1.5h; Sealed tube;

Reference： [1]Current Patent Assignee: XINXIANG MEDICAL UNIVERSITY - CN113443970, 2021, A Location in patent: Paragraph 0038-0040
[2]Zhu, Runqing; Sun, Qianqian; Li, Jing; Li, Luohao; Gao, Qinghe; Wang, Yakun; Fang, Lizhen [Chemical Communications, 2021, vol. 57, # 97, p. 13190 - 13193]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	103-16-2	MDL No. :	MFCD00002333
Formula :	C₁₃H₁₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VYQNWZOUAUKGHI-UHFFFAOYSA-N
M.W :	200.23	Pubchem ID :	7638
Synonyms :	Benoquin	Chemical Name :	4-benzyloxyphenol

Num. heavy atoms :	15
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.08
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	59.44
TPSA :	29.46 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.09 cm/s

Log Po/w (iLOGP) :	2.25
Log Po/w (XLOGP3) :	3.43
Log Po/w (WLOGP) :	2.82
Log Po/w (MLOGP) :	2.69
Log Po/w (SILICOS-IT) :	2.92
Consensus Log Po/w :	2.82

[ CAS No. 103-16-2 ] {[proInfo.proName]}

Quality Control of [ 103-16-2 ]

Related Doc. of [ 103-16-2 ]

Product Details of [ 103-16-2 ]

Calculated chemistry of [ 103-16-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 103-16-2 ]

Application In Synthesis of [ 103-16-2 ]

[ 103-16-2 ] Synthesis Path-Upstream 1~7

[ 103-16-2 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-3.64
Solubility :	0.0463 mg/ml ; 0.000231 mol/l
Class :	Soluble
Log S (Ali) :	-3.73
Solubility :	0.0374 mg/ml ; 0.000187 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.49
Solubility :	0.00649 mg/ml ; 0.0000324 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.5

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P272-P280-P302+P352-P305+P351+P338-P333+P313-P337+P313-P362+P364-P501	UN#:	N/A
Hazard Statements:	H316-H317-H319	Packing Group:	N/A
GHS Pictogram:

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