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

HRID 376303
Notes
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Reaction equation

HRID 376303 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 10755891(3-Chloro-4-fluorophenyl)[4-fluoro-4-(hydroxymethyl)-1-piperidinyl]methanone

Product 1

HCID 10718129toluene-4-sulfonic acid 1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl-methyl EsterYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

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

  1. temperaturemaintained under a nitrogen atmosphere
  2. additionit is poured into ice-cold water
  3. extractionextracted with chloroform
  4. washthe organic phase is washed with a 1N aqueous solution of hydrochloric acid
  5. dry with materialThe organic phase is dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes