Chlorosulfonic acid → 3-chloro-4-[[(2R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propanoyl]amino]benzenesulfonyl chloride
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:17])[C@:10]([OH:16])([CH3:15])[C:11]([F:14])([F:13])[F:12].[Cl:18][S:19](O)(=[O:21])=[O:20]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([S:19]([Cl:18])(=[O:21])=[O:20])[CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:17])[C@:10]([OH:16])([CH3:15])[C:11]([F:13])([F:12])[F:14]Participants
Conditions
- Temperature
- 85 °C
Procedure
(R)-N-(2-Chlorophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Method 74) (13.8 g, 52 mmol) was added in portions to a cooled (0° C.) solution of chlorosulphonic acid (25 ml) over 15 mins and then the mixture was heated to 85° C. After 4.5 h the reaction mixture was cooled in an ice bath and then poured very slowly onto a stirred ice-water mixture. After stirring for 15 mins. the mixture was extracted with ethyl acetate (2×100 ml) and the combined organic layer washed with brine, dried and concentrated to yield a brown oil. This oil was purified by flash column chromatography using 10:1, iso-hexane: ethyl acetate to yield the title compound as a pale yellow solid (11 g, 30 mmol). NMR: 1.6 (s, 3H), 7.55 (dd, 1H), 7.6 (d, 1H), 7.95 (d, 1H), 9.7 (brs, 1H); MS: 364.
Workup
- temperatureAfter 4.5 h the reaction mixture was cooled in an ice bath
- extractionthe mixture was extracted with ethyl acetate (2×100 ml)
- washthe combined organic layer washed with brine
- customdried
- concentrationconcentrated
- customto yield a brown oil
- customThis oil was purified by flash column chromatography
Sources & evidence
- ORD record
- ord-8815f23e537140118ceebd7fb4824bc4
- Source dataset
- uspto-grants-2002_12
- Patent number
- US06498275B1
Reaction notes
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