4-Toluenesulfonyl chloride → toluene-4-sulfonic acid 1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl-methyl Ester

HRID 376303Notes

Reaction equation

[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[F:12][C:13]1([CH2:29][OH:30])[CH2:18][CH2:17][N:16]([C:19]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=2)=[O:20])[CH2:15][CH2:14]1>N1C=CC=CC=1>[Cl:28][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][C:24]=1[F:27])[C:19]([N:16]1[CH2:17][CH2:18][C:13]([CH2:29][O:30][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])([F:12])[CH2:14][CH2:15]1)=[O:20]

Participants

Conditions

Temperature: 0 °C

Procedure

4.87 g of para-toluenesulfonyl chloride (25.5 mmol) are slowly added to a solution of 6.70 g of (4-fluoro-4-hydroxymethylpiperidin-1-yl)-(3-chloro-4-fluorophenyl)methanone (23.12 mmol) in 40 ml of pyridine cooled to 0° C. and maintained under a nitrogen atmosphere. The mixture is stirred for 12 hours at room temperature and then it is poured into ice-cold water, extracted with chloroform and then the organic phase is washed with a 1N aqueous solution of hydrochloric acid. The organic phase is dried over magnesium sulfate, filtered and then concentrated under vacuum. The title product is purified by recrystallization from a dichloromethane/diisopropyl ether mixture. 7.73 g of a white crystalline powder are obtained.

Workup

temperaturemaintained under a nitrogen atmosphere
additionit is poured into ice-cold water
extractionextracted with chloroform
washthe organic phase is washed with a 1N aqueous solution of hydrochloric acid
dry with materialThe organic phase is dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated under vacuum
customThe title product is purified by recrystallization from a dichloromethane/diisopropyl ether mixture

Sources & evidence

ORD record: ord-6e396fbc82ea49309e020cb61aff24ea
Source dataset: uspto-grants-2000_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06020345

Reaction notes

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