Name: 85117-99-3|2-(Bromomethyl)-1,4-difluorobenzene|98%
Brand: Ambeed
SKU: A172864
Price: 5.0 USD
Availability: InStock
Rating: 99 (32 reviews)

1
[ 452-67-5 ]
[ 85117-99-3 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1005 - 1009
[2]Journal of the Chemical Society. Perkin transactions I,1997,p. 2903 - 2909
[3]Angewandte Chemie - International Edition,2012,vol. 51,p. 4594 - 4597

2
[ 98273-79-1 ]
[ 85117-99-3 ]
[ 188622-52-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1997,vol. 34,p. 27 - 32

3
[ 85117-99-3 ]
[ 485-71-2 ]
(1S,2S,4S,5R)-1-(2,5-Difluoro-benzyl)-2-((R)-hydroxy-quinolin-4-yl-methyl)-5-vinyl-1-azonia-bicyclo[2.2.2]octane; bromide [ No CAS ]

Reference： [1]Organic letters,2002,vol. 4,p. 4245 - 4248

4
[ 78342-42-4 ]
[ 85117-99-3 ]
[ 837430-10-1 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151

5
[ 106-54-7 ]
[ 85117-99-3 ]
[ 470716-52-0 ]

Yield	Reaction Conditions	Operation in experiment
99.6%		4-Chlorothiophenol (253g, 1. [75MOL)] was dissolved in industrial methylated spirits (1265mL) and 2M sodium hydroxide solution [(901ML)] was added, maintaining the temperature below [20C.] A solution of 2,5- difluorobenzyl bromide (355g, 1. [72MOL)] in industrial methylated spirits (250mL) was added dropwise to the [THIOLATE] solution, maintaining the temperature below [15C.] Upon completion of the reaction, water (lOOOmL) was added. The resulting slurry was aged at [5C] and then filtered. The cake was washed sequentially with cold industrial methylated spirits: water (40: 60) and then water (500mL). Drying [IL7.] vacuo at ambient temperature furnished 2- [ [ (4-chlorophenyl) thio] methyl]- 1, [4-DIFLUOROBENZENE] (462.3g, 99. [6%). 1H] NMR [(CDC13)] 7.23 (4H, s), 6.69- 6.86 (3H, [M)] and 4.04 (2H, s).
98%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 3h;	After addition of potassium carbonate (4.00 g, 29.0 mmol) and <strong>[85117-99-3]2-bromomethyl-1,4-difluorobenzene</strong> (5.00 g, 24.2 mmol) to a solution of 4-chlorobenzenethiol (3.86 g, 26.6 mmol) in N,N-dimethylformamide (120 ml), the mixture was stirred for 3 hours at room temperature. To the reaction mixture were added saturated ammonium chloride (50 ml) and water (20 ml), followed by extraction with diethyl ether. The extracts were combined, washed with water and brine, dried over MgSO4, and concentrated. The residue thus obtained was purified by chromatography on a silica gel column (1% ethyl acetate-hexane), whereby the title compound (6.41 g, 98%) was obtained as a colorless oil.1H-NMR (400MHz,CDCl3) delta: 4.04(2H,s), 6.85-7.00(3H,m), 7.23(4H,s).
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h;Product distribution / selectivity;	After addition of potassium carbonate (4.00 g, 29.0 mmol) and <strong>[85117-99-3]2-bromomethyl-1,4-difluorobenzene</strong> (5.00 g, 24.2 mmol) to an N,N-dimethylformamide (120 ml) solution of 4-chlorobenzenethiol (3.86 g, 26.6 mmol), the resulting mixture was stirred at room temperature for 3 hours. To the reaction mixture were added saturated ammonium chloride (50 ml) and water (20 ml), followed by extraction with diethyl ether. The extracts were combined, washed with water and brine, dried (over MgSO4) and concentrated. The residue thus obtained was purified by silica gel column chromatography (1% ethyl acetate - hexane) to give 2-[(4-chlorophenyl)thiomethyl]-1,4-difluorobenzene (6.41 g, 98%) as a colorless oil.

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 4149 - 4155
[2]Patent: WO2004/13090,2004,A1 .Location in patent: Page 11
[3]Patent: EP1466898,2004,A1 .Location in patent: Page 20
[4]Patent: EP1640366,2006,A1 .Location in patent: Page/Page column 16
[5]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 2685 - 2688
[6]Patent: JP2005/501120,2005,A .Location in patent: Page/Page column 12

6
[ 14752-66-0 ]
[ 85117-99-3 ]
[ 470716-51-9 ]

Yield	Reaction Conditions	Operation in experiment
87%	With ammonium molybdate; dihydrogen peroxide; In butan-1-ol; for 5h;Heating / reflux;	After addition of <strong>[85117-99-3]2-bromomethyl-1,4-difluorobenzene</strong> (12.3 ml, 95.5 mmol) to a suspension of sodium 4-chlorobenzenesulfinate (19.0 g, 95.5 mmol) in butanol (200 ml), the mixture was heated under reflux for 5 hours. The solid thus precipitated was collected by filtration and dissolved in methylene chloride. The resulting solution was washed with brine, dried over MgSO4, and concentrated. The solid thus obtained was recrystallized from hexane, whereby the title compound (12.3 g, 43%) was obtained as colorless needle crystals. The filtrate was extracted with methylene chloride. The extract was washed with water and brine, dried over MgSO4, and concentrated. The solid thus obtained was washed with hexane, and dissolved in diethyl ether. After removal of an insoluble matter, the residue was concentrated. The solid was recrystallized from hexane, whereby the title compound (12.7 g, 44%) was obtained.IR (ATR) nu: 3089, 2991, 2943, 1581, 1496, 1315, 1279, 1213, 1149, 1090, 1080, 1012, 958, 816, 779, 756, 729, 708, 646, 517, 469 cm-1.1H-NMR (400MHz, CDCl3) delta: 4.36(2H,s), 6.91(1H,td,J=9.0,4.4Hz), 6.99-7.06(1H,m), 7.11(1H,ddd,J=8.3,5.6,3.2Hz), 7.45(2H,d,J=8.8Hz), 7.62(2H,d,J=8.8Hz). MS (m/z) : 303 (M++H).
43%	In butan-1-ol; for 5h;Heating / reflux;Product distribution / selectivity;	To a butanol (200 ml) suspension of sodium 4-chlorobenzenesulfinate (19.0 g, 95.5 mmol) was added <strong>[85117-99-3]2-bromomethyl-1,4-difluorobenzene</strong> (12.3 ml, 95.5 mmol). The resulting mixture was heated under reflux for 5 hours. The solid thus precipitated was collected by filtration, and dissolved in methylene chloride. The resulting solution was washed with brine, dried (over MgSO4). After concentration, the solid thus obtained was recrystallized from hexane to give the title compound (12.3 g, 43%) as colorless needle crystals.

Reference： [1]Patent: EP1466898,2004,A1 .Location in patent: Page 20; 21
[2]Patent: EP1640366,2006,A1 .Location in patent: Page/Page column 16

7
[ 85117-99-3 ]
[ 522651-57-6 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; magnesium; In diethyl ether; for 1.66667h;Heating / reflux;	To a suspension of magnesium strip (763 mg) in diethyl ether (7 mL) was added iodine (one crystal) followed by 0.4 mL of 2- (bromomethyl)-1, 4-difluorobenzene under nitrogen. The reaction was initiated with a heat gun and 2-(bromomethyl)-1, 4-difluorobenzene (5.0 g, 24.25 mmol) in diethyl ether (7 mL) was added slowly. After addition was completed the reaction mixture was refluxed for 100 minutes, cooled to room temperature.

Reference： [1]Patent: WO2005/61499,2005,A1 .Location in patent: Page/Page column 24

8
[ 868636-95-7 ]
[ 85117-99-3 ]
methyl 4-[(1S)-1-({5-chloro-2-[(2,5-difluorobenzyl)oxy]benzoyl}amino)ethyl]benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 18 - 25℃;	A mixture of 4-{(1S)-1-[(5-chloro-2-hydroxybenzoyl)amino]ethyl}benzoate (step 4 of Example 8, 100 mg, 0.30 mmol), <strong>[85117-99-3]2-(bromomethyl)-1,4-difluorobenzene</strong> (62 mg, 0.30 mmol), and potassium carbonate (83 mg, 0.60 mmol) in N,N-dimethylformamide was stirred at room temperature overnight. To the mixture was added water and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by flash column chromatography on silica gel eluding with hexane/ethyl acetate (3/1) to afford 130 mg (94%) of the title compound: MS (ESI) m/z 460 (M+H)+, 458 (M-H)-.

Reference： [1]Patent: US2005/250818,2005,A1 .Location in patent: Page/Page column 31

9
[ 67679-83-8 ]
[ 85117-99-3 ]
C₁₇H₂₂F₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With zinc;bis-triphenylphosphine-palladium(II) chloride; In diethylene glycol dimethyl ether; at 0℃; for 1h;Product distribution / selectivity;	A benzyl compound of the present invention was prepared in the same manner as in Example 1 except for using 2,5-difluoro benzyl bromid as a starting material, and using 0.44 mmol of bis(triphenylphosphine)palladium-(II)chloride, and 88 mmol of zinc as a catalyst. Yield and selectivity of the objective benzyl ketone were shown in table 1. MS [m/z] 153 (Pr-Cyc-CO+), 127 (F2-Aryl-CH2+), 125 (Pr-Cyc+), 83 (C6H11+), 69 (C5H9+), 55 (C9H7+), 41 (C3H5+)
63 - 77%	With zinc;palladium diacetate; triphenylphosphine; In diethylene glycol dimethyl ether; at 0 - 25℃; for 1h;Product distribution / selectivity;	A benzyl compound of the present invention was prepared in the same manner as in Example 1 except for using 2,5-difluoro benzyl bromid as a starting material. Yield and selectivity of the objective benzyl ketone are shown in table 1.MS [m/z] 153 (Pr-Cyc-CO+), 127 (F2-Aryl-CH2+), 125 (Pr-Cyc+), 83 (C6H11+), 69 (C5H9+), 55 (C4H7+), 41 (C3H5+) A benzyl compound of the present invention was prepared in the same manner as in Example 1 except for using 2,5-difluoro benzyl bromid as a starting material, and controlling temperature in the reaction vessel so as to be at 25 C. Yield and selectivity of the objective benzyl ketone are shown in table 1.MS [m/z] 153 (Pr-Cyc-CO+) , 127 (F2-Aryl-CH2+), 125 (Pr-Cyc+), 83 (C6H11+), 69 (C5H9+), 55 (C4H7+), 41 (C3H5+)

Reference： [1]Patent: EP1609774,2005,A1 .Location in patent: Page/Page column 16; 22
[2]Patent: EP1609774,2005,A1 .Location in patent: Page/Page column 15; 22

10
[ 1663-39-4 ]
[ 85117-99-3 ]
[ 944950-16-7 ]
[ 944950-15-6 ]

Yield	Reaction Conditions	Operation in experiment
	With tributyl-amine; lithium chloride;palladium diacetate; In N,N-dimethyl-formamide; at 45 - 120℃;Sealed tube;	To a solution of LiCI (3.39 g, 80 mmol) and palladium (II) acetate (450 mg, 2.0 mmol) in DMF (75 mL) in a sealed tube was added 2,5-difluorobenzylbromide (9.65 mL, 75 mmol), tert-btylacrylate (11.9 mL, 82 mmol) and tributylamietae (19.5 mL, 82 mmol). The reaction was then stirred 2 h at 45C and overnight at 1200C. The cooled <n="65"/>solution was taken up in Et2theta, washed with water and brine, dried and concentrated. The residue was purified by flash-chromatography over silica gel (eluted with hexanes/DCM 75:25 to DCM) to give 9.26 g (49%) of alkene.

Reference： [1]Patent: WO2007/84595,2007,A2 .Location in patent: Page/Page column 62-63

11
4-(7-bromo-3H-benzoimidazole-5-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxylic acid ethyl ester [ No CAS ]
[ 85117-99-3 ]
[ 631911-52-9 ]
[ 631911-51-8 ]

Yield	Reaction Conditions	Operation in experiment
55%	With ammonia; potassium carbonate; In methanol; dichloromethane; N,N-dimethyl-formamide;	a 4-[7-Bromo-3-(2,5-difluoro-benzyl)-3H-benzoimidazole-5-sulfonyl]-5-methylsulfanyl-thiophene-2-carboxylic acid ethyl ester and 4-[7-Bromo-1-(2,5-difluoro-benzyl)-1H-benzoimidazole-5-sulfonyl]-5-methylsulfanyl-thiophene-2-carboxylic acid ethyl ester The procedure as in Example 39: step a was followed using 4-(7-bromo-3H-benzoimidazole-5-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxylic acid ethyl ester (100 mg, 0.217 mmol, Example 38: step e), 2-bromomethyl-1,4-difluoro-benzene (28 muL, 0.217 mmol), K2CO3 (60 mg, 0.434 mmol), and DMF (3 mL). The crude was purified by preparative TLC (2-4% 2.0 M NH3 in methanol/CH2Cl2) to afford a mixture of 4-[7-bromo-3-(2,5-difluoro-benzyl)-3H-benzoimidazole-5-sulfonyl]-5-methylsulfanyl-thiophene-2-carboxylic acid ethyl ester and 4-[7-bromo-1-(2,5-difluoro-benzyl)-1H-benzoimidazole-5-sulfonyl]-5-methylsulfanyl-thiophene-2-carboxylic acid ethyl ester as a brown oil (70 mg, 55%). This mixture was used directly in the next step. ESI-MS (m/z): Calcd. for C21H15BrF2N2O4S3: 586.0 (M+1); found: 588.9.

Reference： [1]Patent: US2004/9995,2004,A1

12
[ 1034835-84-1 ]
[ 85117-99-3 ]
[ 1034354-96-5 ]

Yield	Reaction Conditions	Operation in experiment
	With C13H30N4PPol; In N,N-dimethyl acetamide; at 70℃;	A 20 mL scintillation vial was charged with PS-BEMP resin (157 mg, 0.35 mmol.). To the resin was then added Example 1A (88 mg, 0.29 mmol) dissolved in DMA (1.0 mL). To the resin-suspension was then added <strong>[85117-99-3]2-(bromomethyl)-1,4-difluorobenzene</strong> (72 mg, 0.35 mmol) dissolved in DMA (0.9 mL). The vial was capped and heated at 70 C. overnight on a heater-shaker. The vial was removed from the heater-shaker and the resin-suspension was filtered out. The reaction mixture was checked by LC/MS and concentrated to dryness. The residue was dissolved in 1:1 DMSO/MeOH and purified by reverse phase HPLC using a method analogous to that described in Example 41 to provide the title compound. 1H NMR (500 MHz, DMSO-D6/D2O) delta ppm 1.38-1.48 (m, 6H) 3.52-3.56 (m, 2H) 3.77-3.80 (m, 3H) 4.83-4.90 (m, 2H) 7.12 (d, 1H) 7.20-7.35 (m, 3H) 7.47 (dd, 1H) 7.62 (d, 1H); MS (ESI), 425 (M+H)+.

Reference： [1]Patent: US2008/153883,2008,A1 .Location in patent: Page/Page column 29

13
[ 1037763-72-6 ]
[ 85117-99-3 ]
[ 1037763-75-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With caesium carbonate;tetra-(n-butyl)ammonium iodide; In N,N-dimethyl-formamide; at 0 - 20℃; for 0.75h;	Step G - Synthesis of Compound 59G; To a solution of compound 59F (130 mg, 0.400 mmol) in 5 mL of dry DMF at 0 0C were added <strong>[85117-99-3]2,5-drifluorobenzyl bromide</strong> (99 mg, 0.480 mmol), cesium carbonate (391 mg, 1.200 mmol) and tetrabutylammonium iodide (10 mg, catalytic). The resulting reaction was allowed to stir at 0 0C for 45 minutes, then warmed to room temperature. The mixture was then diluted with ethyl acetate (80 mL), and the resulting solution was sequentially washed with water (10 mL) and brine (10 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to provide a crude residue which was purified using column chromatography on silica gel (Biotage 25-S column; gradient: 0 to 25% ethyl acetate in hexanes) to provide compound 59G(140 mg, 78 %) as a white solid. M.S. found for C25H20F2N2O4: 451.12 (M+H)+.

Reference： [1]Organic Letters,2012,vol. 14,p. 556 - 559
[2]Patent: WO2008/82484,2008,A1 .Location in patent: Page/Page column 167

14
[ 1037762-64-3 ]
[ 85117-99-3 ]
[ 1037762-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;	Step E - Synthesis of Compound 12E; 2,4-difluorobenzylbromide (0.187 g, 1.5 eq ) was added dropwise to a allowed to stirsolution of compound 12D (202 mg, 0.6 mmol) and Cs2CO3 in DMF at room temperature under an atmosphere of nitrogen. After 16 hours, the reaction mixture was partitioned between EtOAc and water. The aqueous phase was separated, washed with water three times, dried (MgSO4) and concentrated. The residue was purified using flash column chromatography on silica gel (EtOAc:Hexane=l:20) to provide compound 12E (0.263 g) as a white solid. MS found for C27H24N2O3 = 463.18 (M+H).

Reference： [1]Patent: WO2008/82484,2008,A1 .Location in patent: Page/Page column 124

15
[ 1037206-35-1 ]
[ 85117-99-3 ]
[ 1037206-38-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	With caesium carbonate;tetra-(n-butyl)ammonium iodide; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h;	Step E - Synthesis of Compound 20F; To a 0 0C solution of 2OE (350 mg, 1.03 mmol) in DMF (11 mL) was added 2,5- drifluorobenzyl bromide (234 mg, 1.13 mmol) and cesium carbonate (1.00 g, 3.08 mmol), with stirring. The ice-bath was removed, and a catalytic amount of tetrabutylammonium iodide (approx. 20 mg) was added. The reaction was stirred at room temperature for 2 hours, then diluted with ethyl acetate (200 mL). The resulting solution was washed with water (3 X 45 mL) and brine (80 mL) sequentially. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to provide a crude residue which was purified using column chromatography on silica gel (Biotage 25-S column; gradient: 0 to 25% ethyl acetate in hexanes) to provide compound 2OF (380 mg, 80 %).

Reference： [1]Patent: WO2008/82488,2008,A1 .Location in patent: Page/Page column 139; 141

16
[ 1040542-76-4 ]
[ 85117-99-3 ]
[ 1040545-28-5 ]

Yield	Reaction Conditions	Operation in experiment
71%		Sodium hydride (53 mg, 1.33 mmol) was added to a solution of the compound from example 14a) (120 mg, 0.53 mmol) in N,N-Dimethylformamide (DMF) (2.5 mL) at 0 C. The reaction was brought to room temperature and stirred for 30 minutes. The temperature was then reduced to 0 C and 2,5-difluorobenzyl bromide (0.07 mL, 0.53 mmol) was added. The reaction was brought to room temperature and stirred for 3 h followed by the addition of IN HCl. The solution was diluted with EtOAc and f^O and the layers separated. The aqueous layer was backextracted with EtOAc several times. The combined organic layers were washed with Brine, dried (MgSO^, filtered and concentrated. The product was purified by column chromatography (SiO2, 15-30% EtOAc/Hexanes) give the title compound (133 mg, 71%). IH NMR (400 MHz, DMSO-(Z6) delta ppm 12.35 (s, 1 H) 7.28 (td, J=9.22, 4.55 Hz, 1 H) 7.15 - 7.25 (m, 1 H) 7.05 (ddd,J=8.84, 5.68, 3.16 Hz, 1 H) 5.18 (s, 2 H) 4.27 (q, J=7.07 Hz, 2 H) 3.15 (sept, J=6.82 Hz, 1 H) 1.26 (t, J=7.07 Hz, 3 H) 1.13 (d, J=6.82 Hz, 6 H).

Reference： [1]Patent: WO2008/89052,2008,A2 .Location in patent: Page/Page column 62

17
[ 610-78-6 ]
[ 85117-99-3 ]
[ 944506-27-8 ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h;	To Example 86a (2.2 g, 10.4 mmol) in DMF (50 mL) was added 4-chloro-3-nitro- phenol (1.8 g, 10.4 mmol), and K2CO3 (2.87 g, 20.8 mmol). The mixture was heated at 80 C for 16 h. The reaction was cooled and poured into water. The aqueous phase was extracted with ethyl acetate (2x) and the combined phases were washed with water, brine, and dried over sodium sulfate. The organic phase was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90: 10) to give the title compound (2.48 g, 66 %).

Reference： [1]Patent: WO2008/133753,2008,A2 .Location in patent: Page/Page column 121

18
[ 75853-20-2 ]
[ 85117-99-3 ]

Yield	Reaction Conditions	Operation in experiment
50%	With phosphorus tribromide; In dichloromethane; at 20℃; for 16h;	To a solution of (2,5-difluoro-phenyl)-methanol (4.8 g, 33.6 mmol) in dichloromethane (40 mL) was added drop wise phosphorus tribromide (94 g, 33.6 mmol) .The mixture was stirred at room temperature for 16 h. The reaction was poured onto ice/water. The aqueous phase was made basic with sodium bicarbonate. The aqueous phase was extracted with <n="122"/>dichloromethane. The organic phase was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10) to give the title compound (3.5g, 50 %).

Reference： [1]Patent: WO2008/133753,2008,A2 .Location in patent: Page/Page column 120-121

19
[ 3612-20-2 ]
[ 85117-99-3 ]
[ 644967-96-4 ]

Yield	Reaction Conditions	Operation in experiment
55%		To a stirring suspension of magnesium strip (763 mg) in diethyl ether (7 mL) was added a crystal of iodine followed by (0.4 mL of <strong>[85117-99-3]2-(bromomethyl)-1,4-difluorobenzene</strong> under nitrogen. The reaction mixture was initiated with a high intensity heat gun, <strong>[85117-99-3]2-(bromomethyl)-1,4-difluorobenzene</strong> 5.0 g, 24.25 mmol) in diethyl ether (7 mL) was added slowly maintaining gentle reflux. After addition was completed the reaction mixture was stirred at reflux for 100 min, cooled to room temperature. To this reaction mixture a solution of 1-benzylpiperidin-4-one (4.57 g, 24.25 mmol) in diethyl ether (12 mL) was added dropwise with vigorous stirring. After addition was completed the reaction mixture was left at room temperature overnight. Aqueous NH4Cl solution was added and stirred at room temperature until hydrolysis was completed, extracted with diethyl ether. The organic layer was washed with H2O, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography (0-1% methanol in dichloromethane, 0.2% NH4OH) to give intermediate 1-benzyl-4-(2,5-difluorobenzyl)piperidin-4-ol (2.74 g) containg large quantities of unknown impurities. To a suspension of NaH (55%, 1.12 g, 26.0 mmol) in toluene (10 mL) was slowly added a solution of 1-benzyl-4-(2,5-difluorobenzyl)piperidin-4-ol in toluene (15 mL). After addition was completed the reaction mixture was stirred at 110C (in a pre heated oil bath), after 5 min, DMF (9 mL) was added and stirring was continued at reflux temperature for 2h. The reaction mixture was cooled to room temperature, H2O (20 mL) was added and extracted with ethyl acetate. The organic layer was dried over Na2SO4,] filtered and concentrated. The residue was purified by silica gel flash chromatography (0-1.5% methanol in dichloromethane, 0.2% NH4OH) to give the subtitled compound (190 mg). 1H-NMR (CDCl3,400 MHz): delta 7.39-7.26 (m, 5H) ; 6.88-6.76 (m, 2H); 6.67 (d, J= 4.2, 8.7 Hz, 1H); 3.59 (s, 2H); 2.99 (s, 2H); 2.68-2.47 (m, 4H); 2.03-1.94 (m, 2H); 1.86-1.76 (m, 2H). APCI-MS: m/z 298 (MH+).

Reference： [1]Patent: WO2004/5295,2004,A1 .Location in patent: Page 54-55; 109-110

20
[ 1126422-61-4 ]
[ 85117-99-3 ]
[ 1126422-63-6 ]

Yield	Reaction Conditions	Operation in experiment
		Step 4:; 5D 5E; A solution of indole derivative 5D (6.5 g, 15.237 mmol) in 50 mL of dry THF was added to an ice-cooled suspension of sodium hydride (1.3 eq, 792 mg of 60% suspension in mineral oil) in 50 mL of dry THF. The resulting solution was stirred for 10 min followed by addition of 2,5-difluorobenzyl bromide (1.3 eq, 2.54 mL, d 1.613). A catalytic amount of tetrabutylammonium iodide (0.2 eq, 1.12 g) was added to the reaction mixture and stirring was <n="108"/>continued for 18 h (temperature from 0 to 25 0C). The reaction was quenched by addition of water (10 mL) and the mixture was diluted with ethyl acetate (500 mL). The organic layer was washed with water (2 x 100 mL) and brine (80 mL), dried over magnesium sulfate, filtered and concentrated to afford the crude product 5E as a colorless foam contaminated with undesired bis-N,O-difluorobenzyl product. The crude mixture was used for next reaction without further any further purification.
	With caesium carbonate;tetra-(n-butyl)ammonium iodide; In N,N-dimethyl-formamide; for 0.5h;Product distribution / selectivity;	Step 4:; A solution of indole derivative 7D (4.0 g, 9.376 mmol) in 90 mL of dry DMF was ice- cooled and treated with 2,5-difluorobenzyl bromide (1.1 eq, 1.32 mL, d 1.613) and cesium carbonate (3.0 eq, 9.16 g). The mixture turned yellow in color and the ice- water bath was removed. A catalytic amount of tetrabutyl ammonium iodide (approx 20 mg) was added. The reaction mixture was stirred for 30 min where it became green in color and TLC (20% ethyl acetate in hexanes) showed no more starting materials left. The reaction was quenched by addition of water (10 mL) and the mixture was diluted with ethyl acetate (400 mL). The organic layer was washed with water (3 x 80 mL) and brine (80 mL), dried over magnesium <n="118"/>sulfate, filtered and concentrated to afford the crude product 7E. The crude mixture was used for next reaction without further any further purification.

Reference： [1]Patent: WO2009/32123,2009,A2 .Location in patent: Page/Page column 106-107
[2]Patent: WO2009/32123,2009,A2 .Location in patent: Page/Page column 106-107

21
[ 1132610-98-0 ]
[ 85117-99-3 ]
[ 1132610-99-1 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 5h;	Step 5: D5; To a solution of compound D4 (300 mg, 0.85 mmol) in DMF (10 mL) was added cesium carbonate (569 mg, 1.75 mmol) and 2,5-difluorobenzyl bromide (351 mg, 1.72 mmol) and the resulting reaction was allowed to stir at room temperature for 5 hours. The reaction mixture was then diluted with EtOAc (250 mL) and washed with brine (2 x 100 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to provide a crude residue which was purified using flash column chromatography on silica gel (EtOAc/Hexanes 0 to 20%) to provide compound D5 as a colorless solid.

Reference： [1]Patent: WO2009/32125,2009,A1 .Location in patent: Page/Page column 91

22
[ 1154603-25-4 ]
[ 85117-99-3 ]
[ 1154603-26-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; for 3h;	To a solution of 3-(l-tert-butoxycarbonyl-2,4-dioxo-1,2-dihydro-4//-thieno[3,4- d]pyrimidin-3-yl)-5-trifluoromethyl-l//-indoIe-2-carboxylic acid tert-butyl ester 51 (30 mg, 0.054 mmoi) in anhydrous THF (1 mL) and anhydrous DMF (1 mL) was added potassium ten- butoxide (9 mg, 0.080 mmol) and 2,5-difluorobenzyl bromide 5J (14.6 mg, 0.071 mmol). The reaction mixture was stirred at room temperature for 3 hours. Ethyl acetate (50 mL) was added and the organic layer was washed with saturated ammonium chloride solution and brine. The organic layer was dried over sodium sulfate. The organic solvent was removed under reduced pressure to provide 3-(l-/m-butoxycarbonyl-2,4-dioxo-1,2-dihydro-4//-thieno[3,4- d]pyrimidin-3-yl)- 1 -(2,5-difluorobenzyl)-5-trifluoromethyl- 1 H-indole-2-carboxylic acid tert- butyl ester 5K which was used in the next step without further purification.

Reference： [1]Patent: WO2009/64848,2009,A1 .Location in patent: Page/Page column 125; 128-129

23
[ 214210-21-6 ]
[ 85117-99-3 ]
[ 1108745-26-1 ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 3098 - 3100
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3392 - 3408

24
[ 623-43-8 ]
[ 85117-99-3 ]
[ 944950-21-4 ]

Yield	Reaction Conditions	Operation in experiment
45%		To a solution of magnesium turnings (7.0 g; 290 mmol) in Et2theta (40 mL) were added a hexane solution containing a catalytic amount of iodine and dibromoethane (1 ml_).The reaction was heated to 400C and a solution of 2, 5-difluorobenzyl bromide (15.0 g, 72.4 mmol) in Et2O (40 mL) was added over 1 h. The reaction mixture was then stirred another hour at 400C then cooled and diluted with Et2O to 100 mL to provide a benzyl Grignard reagent solution (16.7 g).To a solution of Cu (I) iodide (4.6 g, 24.1 mmol) in THF (80 mL) was added N,N,N',N'-tetramethylethylenediamine (4.0 mL, 26.6 mmol) and the reaction mixture was stirred for 15 minutes at RT. The mixture was then cooled to -78C and the benzyl Grignard solution prepared above (5 g, 21.6 mmol) in Et2O (30 mL) was added to the mixture, followed by 15 minutes of stirring. A solution of TMSCI (6.0 mL, 60.4 mmol) and trans-methyl crotonate (2.0 mL, 21.7 mmol) in THF (30 mL) was then added and the reaction mixture was allowed to warm to -500C and stirred at -5O0C overnight. The crude product was poured into a saturated solution of NH4OH and NH4CI, extracted with Et2O, washed with water and dried over sodium sulfate. The crude product obtained after concentration was purified by chromatography over silica gel (eluted with hexanes/EtOAc 95:5) to give 2.5 g (45%) of ester.

Reference： [1]Patent: WO2007/84595,2007,A2 .Location in patent: Page/Page column 77

25
C₂₀H₂₂N₂O₃ [ No CAS ]
[ 85117-99-3 ]
[ 1080568-71-3 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere;	2,5-difluorobenzylbromide (0.187 g, 1.5 eq) was added drop wise to a stirred solution of compound 3F (202 mg, 0.6 mmol) and Cs2CO3 (294 mg, 1.5 eq) in DMF (4 mL) and the resulting reaction was allowed to stir at room temperature under an atmosphere of nitrogen for 16 hours. The reaction mixture was then partitioned between EtOAc and water and the aqueous phase was separated, washed with water (3×), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified using flash column chromatography on silica gel (EtOAc:Hexane=1:20) to provide compound 3G (0.263 g) as a white solid. MS found for C27H24F2N2O3S: 493.23 (M+H)+. 1H NMR (400 MHz, CDCl3) 8.21 & 8.20 (dd, J=2.20 & 5.13 Hz, 1H), 7.66 & 7.65 (dd, J=2.20 & 7.32 Hz, 1H), 7.26 (s, 1H), 7.15 (s, 1H), 7.07-6.99 (m, 2H), 6.90-6.84 (m, 1H), 6.42-6.38 (m, 1H), 5.83 (s, 2H), 4.07 (q, J=7.32 Hz, 2H), 3.87 (s, 3H), 2.98-2.90 (m, 4H), 2.09 (quintet, J=7.32 Hz, 2H), 0.95 (t, J=7.32 Hz, 3H).

Reference： [1]Patent: US2010/322901,2010,A1 .Location in patent: Page/Page column 57

26
[ 1283135-18-1 ]
[ 85117-99-3 ]
[ 1283135-39-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With tetra-(n-butyl)ammonium iodide; sodium hydride; In N,N-dimethyl-formamide; mineral oil; at -78 - 20℃; for 2.5h;Inert atmosphere;	At -78C under argon atmosphere, NaH (60% dispersion in mineral oil, 17 mg, 0.43 mmol) was added to a solution of 4a (117 mg, 0.387 mmol), 4-chlorobenzyl bromide (95 mg, 0.46 mmol) and tetrabutylammonium iodide (29 mg, 0.077 mmol) in anhydrous DMF (5 mL). The mixture was then warmed to 0C and stirred for 30 min, and further stirred at rt for 30 min. The reaction mixture was quenched with H2O and extracted with EtOAc (2x). The organic layers were dried with MgSO4, filtered, and concentrated. The yellow residue was purified via column chromatography (EtOAc/Hex = 1:2) to give a white solid 5a (116 mg, 0.271 mmol, 70%).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1515 - 1518

27
[ 1296877-19-4 ]
[ 85117-99-3 ]
[ 1296876-78-2 ]

Yield	Reaction Conditions	Operation in experiment
56%		General procedure: To a stirred suspension of 3a-3d (1 mmol) in dimethylsulfoxide (DMSO) (3 mL) at 5-10 C was added potassium t-butoxide (1.2 mmol) in small portions within a period of 10 min. After stirring 30 min appropriate benzyl halide (1 mmol) was added and then stirring was continued at room temperature for 2-3 h. The reaction mixture was quenched with ice cold (5 mL) water and extracted with ethyl acetate (3 × 5 mL), the combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography by using silica gel (60-120 mesh) to give the desired compounds 4-23.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1694 - 1700

28
[ 1296877-21-8 ]
[ 85117-99-3 ]
[ 1296876-88-4 ]

Yield	Reaction Conditions	Operation in experiment
54%		General procedure: To a stirred suspension of 3a-3d (1 mmol) in dimethylsulfoxide (DMSO) (3 mL) at 5-10 C was added potassium t-butoxide (1.2 mmol) in small portions within a period of 10 min. After stirring 30 min appropriate benzyl halide (1 mmol) was added and then stirring was continued at room temperature for 2-3 h. The reaction mixture was quenched with ice cold (5 mL) water and extracted with ethyl acetate (3 × 5 mL), the combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography by using silica gel (60-120 mesh) to give the desired compounds 4-23.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1694 - 1700

29
[ 1296877-23-0 ]
[ 85117-99-3 ]
[ 1296876-98-6 ]

Yield	Reaction Conditions	Operation in experiment
74%		General procedure: To a stirred suspension of 3a-3d (1 mmol) in dimethylsulfoxide (DMSO) (3 mL) at 5-10 C was added potassium t-butoxide (1.2 mmol) in small portions within a period of 10 min. After stirring 30 min appropriate benzyl halide (1 mmol) was added and then stirring was continued at room temperature for 2-3 h. The reaction mixture was quenched with ice cold (5 mL) water and extracted with ethyl acetate (3 × 5 mL), the combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography by using silica gel (60-120 mesh) to give the desired compounds 4-23.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1694 - 1700

30
[ 1296877-25-2 ]
[ 85117-99-3 ]
[ 1296877-09-2 ]

Yield	Reaction Conditions	Operation in experiment
68%		General procedure: To a stirred suspension of 3a-3d (1 mmol) in dimethylsulfoxide (DMSO) (3 mL) at 5-10 C was added potassium t-butoxide (1.2 mmol) in small portions within a period of 10 min. After stirring 30 min appropriate benzyl halide (1 mmol) was added and then stirring was continued at room temperature for 2-3 h. The reaction mixture was quenched with ice cold (5 mL) water and extracted with ethyl acetate (3 × 5 mL), the combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography by using silica gel (60-120 mesh) to give the desired compounds 4-23.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1694 - 1700

31
[ 881170-98-5 ]
[ 85117-99-3 ]
[ 1297284-28-6 ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 16h;Inert atmosphere;	To a 100 mL round bottom flask under a nitrogen atmosphere was added intermediate 2, tert-butyl 2-(5-chloro-2-methyl-3-(4-oxo-3,4-dihydrophthalazin-1-yl)-1H-indol-1-yl)acetate (0.400 g, 0.95 mmol, 1.0 equiv), 2,5-difluorobenzyl bromide (0.390 g, 1.89 mmol, 2.0equiv), potassium carbonate (0.326 g, 2.38 mmol, 2.5 equiv) and 40 mL DMF. The resulting suspension was heated to 85 C. for 16 hours. The mixture was then allowed to cool to room temperature and then poured into 200 mL water. This was extracted with three 50 mL portions of EtOAc. The combined organic layers were washed with water and brine and dried over MgSO4. Filtration and concentration in vacuo gave a tan solid. This crude material was purified by silica gel chromatography to give the desired product as a tan solid (0.338 g, 65%).

Reference： [1]Patent: US2011/105509,2011,A1 .Location in patent: Page/Page column 36

32
[ 123-08-0 ]
[ 85117-99-3 ]
[ 1272111-71-3 ]

Yield	Reaction Conditions	Operation in experiment
71%		General procedure: To a stirred suspension of 4-hydroxy benzaldehyde/4-hydroxy acetophenone (1 mmol) in dimethyl sulfoxide (DMSO) (5 mL) at 5-10 C was added potassium t-butoxide (1.2 mmol) was added in small portions in the period of 10 min. After stirring of 30 min, substituted benzyl/aryl halide (1 mmol) was added and then stirring was continued at room temperature for 4-5 h. The reaction mixture was quenched with ice cold water (5 mL) and extracted with ethyl acetate (3 × 5 mL), the combined organic layers were washed with water (3 × 5 mL) dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography by using silica gel (60-120 mesh) and ethyl acetate: Hexane (4:94) as eluent to give the compounds (2a-f and 14a-f).

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4302 - 4310

33
[ 85117-99-3 ]
[ 99-93-4 ]
[ 187532-84-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In acetonitrile; at 150℃; for 0.0833333h;Sealed vial; Microwave irradiation;	Toa stirred mixture of 2,5-difluorobenzyl bromide (2) (131 muL, 1 mmol), potassium carbonate (145 mg, 1.05 mmol, 1.05 equiv) and 10 mL MeCN in a 20 mL Pyrex microwavevial, 4-hydroxyacetophenone (3) (146 mg, 1.05 mmol, 1.05 equiv) was added. The suspension was stirred for 10 s and sealed with an aluminum crimp and Teflon septum. The reaction mixture was subjected to microwave heating for 5 min (hold time) at 150 C and then cooled to 50 C. The so processed reaction mixture was concentrated under reduced pressure and the residue purified by flash chromatography (eluent - n-hexane/EtOAc; gradient 0 to 20% AcOEt) to afford 4-(2,5-difluorobenzyloxy)acetophenone (4) as a white solid (257 mg, 98%): m.p. = 98- 100 C (2-propanol); 1H-NMR (300 MHz, CDCl3): d = 2.56 (s, 3H), 5.17 (s, 2H), 6.96-7.10 (m, 4H), 7.19-7.25 (m, 1H), 7.96-7.99 (m, 2H); MS (neg. ESI), m/z (%): 261 (100) [M-1].
71%		General procedure: To a stirred suspension of 4-hydroxy benzaldehyde/4-hydroxy acetophenone (1 mmol) in dimethyl sulfoxide (DMSO) (5 mL) at 5-10 C was added potassium t-butoxide (1.2 mmol) was added in small portions in the period of 10 min. After stirring of 30 min, substituted benzyl/aryl halide (1 mmol) was added and then stirring was continued at room temperature for 4-5 h. The reaction mixture was quenched with ice cold water (5 mL) and extracted with ethyl acetate (3 × 5 mL), the combined organic layers were washed with water (3 × 5 mL) dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography by using silica gel (60-120 mesh) and ethyl acetate: Hexane (4:94) as eluent to give the compounds (2a-f and 14a-f).

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3731 - 3734
[2]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4302 - 4310

34
[ 1353676-79-5 ]
[ 85117-99-3 ]
[ 1353676-80-8 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 556 - 559

35
5-[4-(tetr-butyldimethylsilanyloxy)-3-methyl-phenylsulfanyl-methyl]-4-methyl-2-[(4-trifluoromethyl)phenyl]thiazole [ No CAS ]
[ 85117-99-3 ]
C₃₂H₃₄F₅NOS₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: A stirred solution of 6 (300 mg, 0.59 mmol) in anhydrous THF (5 ml) was cooled to -78 C in dryice-acetone bath under N2 atmosphere. 2.0 M lithiumdiisopropylamide (619 mul, 1.24 mmol) was added dropwise to reaction mixture at -78 C. The reaction mixture was stirred at -78 C for 30 min. A solution of benzyl bromide (77 mul, 0.65 mmol) in THF (1 ml) was added dropwise at -78 C. After the mixture was stirred at same temperature for further 30 min, it was quenched by adding sat. NH4Cl solution. The mixture was diluted by ethyl acetate and the organic layer was dried with MgSO4, filtered, and concentrated under reduced pressure to give crude compound. The crude compound was purified by column chromatography on silica gel (n-hexnane/ethylacetate = 10/1) to obtain 7a as colorless oil (265 mg, 75%).

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 53,p. 190 - 202

36
[ 123-31-9 ]
[ 85117-99-3 ]
[ 223104-41-4 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In acetone; at 160℃; for 0.333333h;Microwave irradiation; Sealed vial;	To a stirred mixture of 2,5-difluorobenzyl bromide (2) (622 muL, 4.83 mmol), potassium carbonate (1 g, 7.25 mmol, 1.5 equiv) and 12 mL acetone in a 20 mL Pyrex microwave vial, hydroquinone (2.13 g, 19.32 mmol, 4 equiv) was added. The suspension was stirred for 10 s and sealed with an aluminum crimp and Teflon septum. The reaction mixture was subjected to microwave heating for 20 min (hold time) at 160 C and then cooled to 50 C. The so processed reaction mixture was concentrated under reduced pressure. To the residue 70 mL of cold CHCl3 were added and the formed suspension stirred for 30 min. The precipitates were removed by filtration and the filtrate concentrated under reduced pressure. The oily residue was purified by flash chromatography (eluent - n-hexane/EtOAc; gradient 0 to 30% AcOEt) to afford 4-(2,5-difluorobenzyloxy)phenol (5) as awhite solid (848 mg, 74%).

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 3731 - 3734

37
[ 1206979-33-0 ]
[ 85117-99-3 ]
[ 1421843-69-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; at 60℃; for 48h;	Example 3: 6-((l-(2,5-difluorobenzyl)-lH-pyrazolo[4,3-c]pyridin-6-yl)amino A suspension of 6-chloro-lH-pyrazolo[4,3-c]pyridine (lg, 6.54mmol), 2,5-difluorobenzyl bromide (l . leq) and potassium carbonate (2eq) in acetonitrile (20mL) was heated at 60C for 48h. The resultant mixture was filtered, the filtrate diluted with DCM and washed with H20. The organic phase was collected, dried (hydrophobic frit) and concentrated in vacuo. The resultant residue was purified by column chromatography (petrol:EtOAc) to give 6-chloro-l- (2 , 5 -difluorobenzyl)- 1 H-pyrazo lo [4 , 3 -c]pyridine . A suspension of 6-chloro-l-(2,5-difluorobenzyl)-lH-pyrazolo[4,3-c]pyridine (50mg, 0.18mmol), 2-amino-5-cyanopyridine (l . leq), Xantphos (O.leq), Pd2(dba)3 (O.leq) and cesium carbonate (2eq) in dioxane:H20 (5: 1) (5mL) was heated at 150 C for 30min under microwave irradiation. The resultant mixture was diluted with DCM and washed with H20. The organic phase was collected, dried (hydrophobic frit) and concentrated in vacuo. The resultant mixture was purified by prep. HPLC to give the title compound^1 H NMR (d6- DMSO) delta 10.48 (s, 1H), 8.87 (d, 1H), 8.65 (dd, 1H), 8.24 (s, 2H), 8.01 (dd, 1H), 7.47 (dd, 1H), 7.29-7.35 (m, 1H), 7.20-7.27 (m, 1H), 7.10-7.15 (m, 1H), 5.62 (s, 2H); LC-MS method C, (ES+) 363, RT = 8.02 min.

Reference： [1]Patent: WO2013/17480,2013,A1 .Location in patent: Page/Page column 42

38
[ 78003-43-7 ]
[ 85117-99-3 ]
[ 1351161-32-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 6.5h;Cooling with ice;	Reference Example 23 [4-(2,5-Difluorobenzyloxy)phenyl]ethoxyacetic acid The compound of Reference Example 21 (13.6 g) was dissolved in DMF (200 mL), and potassium carbonate (10.5 g) and 2,5-difluorobenzylbromide (14.6 g) were added thereto under ice cooling. The mixture was stirred for 6.5 hours at room temperature. After distilling off the solvent under reduced pressure, the residue was diluted with a saturated aqueous solution of ammonium chloride, and the mixture was extracted with diethyl ether. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, a crude product was obtained. The crude product thus obtained was dissolved in ethanol (300 mL), and a 10% aqueous solution of sodium hydroxide (100 mL) was added thereto under ice cooling. The mixture was stirred for 11 hours at room temperature. After distilling off the solvent under reduced pressure, the residue was acidified with 2 mol/L hydrochloric acid and extracted with chloroform. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (4% to 10% methanol/chloroform), and thus the title compound (20.0 g) was obtained. 1H-NMR (CDCl3) delta: 1.27 (3H, t, J=7.0 Hz), 3.52-3.62 (2H m), 4.84 (1H, s), 5.11 (2H, s), 6.94-7.09 (4H, m), 7.19-7.25 (1H, m), 7.35-7.38 (2H, m). ESI-MS Found: m/z 321 (M-H)-

Reference： [1]Patent: US2013/65896,2013,A1 .Location in patent: Paragraph 0312-0315

39
[ 637-81-0 ]
[ 10134-91-5 ]
[ 85117-99-3 ]
[ 163105-90-6 ]
[ 1037763-25-9 ]