Hydrochloric Acid → 2-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-benzoic acid

HRID 925259Notes

Reaction equation

[SH:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Br[CH2:12][CH2:13][C:14]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)([F:16])[F:15].C(=O)([O-])[O-].[K+].[K+].Cl>CC(C)=O.O>[F:16][C:14]([F:15])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH2:13][CH2:12][S:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 2-mercapto-benzoic acid (0.10 g, 0.65 mmol) in acetone (30 ml) are added 1-(3-bromo-1,1-difluoro-propyl)-4-fluoro-benzene (0.16 g, 0.65 mmol) and potassium carbonate (0.27 g, 1.95 mmol) at RT. The reaction mixture is stirred at 70° C. for 2.5 h. The reaction mixture is diluted with water (20 ml), acidified with 2M hydrochloric acid and the aqueous layer is extracted with EtOAc (3×20 ml). The combined organic layers are washed with water (15 ml), brine (15 ml), dried over sodium sulfate and evaporated to dryness. The crude product is purified by column chromatography (silica gel, 80% EtOAc/hexane) to yield 2-[[3,3-difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-benzoic acid (0.08 g, 0.24 mmol, 37%).

Workup

extractionthe aqueous layer is extracted with EtOAc (3×20 ml)
washThe combined organic layers are washed with water (15 ml), brine (15 ml)
dry with materialdried over sodium sulfate
customevaporated to dryness
customThe crude product is purified by column chromatography (silica gel, 80% EtOAc/hexane)

Sources & evidence

ORD record: ord-9a05a69ddfdc49daaf341e42d7076f62
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284286B2

Reaction notes

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