Thionyl Chloride → (4'-Chloro-4-methylbiphenyl-3-yl)acetyl chloride
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([CH2:15][C:16]([OH:18])=O)[CH:9]=2)=[CH:4][CH:3]=1.S(Cl)([Cl:21])=O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([CH2:15][C:16]([Cl:21])=[O:18])[CH:9]=2)=[CH:4][CH:3]=1Participants
Conditions
- Temperature
- 80 °C
Procedure
5.00 g (19.18 mmol) of (4′-chloro-4-methylbiphenyl-3-yl)acetic acid (EP 2029531 A1 and US 2009/298828 A1) were dissolved in 36.51 g (306.84 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for four hours and then concentrated under reduced pressure. Drying under fine vacuum gave 5.4 g (100% of theory) of (4′-chloro-4-methylbiphenyl-3-yl)acetyl chloride as a brownish oil. At room temperature, 5.00 g (19.09 mmol) of methyl cis-1-amino-4-(trifluoromethyl)cyclohexanecarboxylate hydrochloride (EP 1220841 A2 and WO 2001/23354 A3), 4.83 g (47.73 mmol) of triethylamine and 117 mg (0.955 mmol) of N,N-dimethylaminopyridine were dissolved in 40 ml of dichloromethane. A solution of 5.33 g (19.09 mmol) of (4′-chloro-4-methylbiphenyl-3-yl)acetyl chloride in 40 ml of dichloromethane was then added dropwise to the mixture. The resulting reaction mixture was stirred at room temperature overnight. For work-up, the mixture was diluted with dichloromethane and the organic phase was washed with aqueous 5% strength citric acid. After drying over sodium sulphate, the mixture was concentrated by evaporation and the residue was purified by chromatography on silica gel (mobile phase: hexane/ethyl acetate gradient). Concentration and drying gave 6.36 g (71% of theory) of the title compound.
Workup
- concentrationconcentrated under reduced pressure
- customDrying under fine vacuum
Sources & evidence
- ORD record
- ord-36f1e04bf22a41ab81d19891a8021c62
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09000026B2
Reaction notes
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