Hydrochloric Acid → (-)-(3S,4R)-3-(3,5-Bis-trifluoromethyl-benzyloxymethyl)-4-(4-fluoro-phenyl)-piperidine hydrochloride

HRID 253082Notes

Reaction equation

HRID 253082 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]([CH2:21][O:22][CH2:23][C:24]2[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=2)[CH2:9]1)=O)(C)(C)C.[ClH:38].CO>>[ClH:38].[F:33][C:30]([F:31])([F:32])[C:28]1[CH:29]=[C:24]([CH:25]=[C:26]([C:34]([F:35])([F:36])[F:37])[CH:27]=1)[CH2:23][O:22][CH2:21][C@H:10]1[C@H:11]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH2:12][CH2:13][NH:8][CH2:9]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 58248364(-)-(3S,4R)-3-(3,5-Bis-trifluoromethyl-benzyloxymethyl)-4-(4-fluoro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 16747664(-)-(3S,4R)-3-(3,5-Bis-trifluoromethyl-benzyloxymethyl)-4-(4-fluoro-phenyl)-piperidine hydrochloride

Procedure

A solution of (−)-(3S,4R)-3-(3,5-bis-trifluoromethyl-benzyloxymethyl)-4-(4-fluoro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (1.10 g, 2.05 mmol) in a 1.25 M solution of hydrochloric acid in methanol (16.4 ml, 3.3 mmol) was stirred for 30 min. at 40° C. The reaction mixture was concentrated to dryness and the residue was partitioned between tert-butyl methyl ether and a 1 M aqueous sodium hydroxide solution. After extraction with three portions of tert-butyl methyl ether the combined organic layers were dried over sodium sulfate and concentrated in vacuo to 0.890 g (99.5%) of the title compound as a colorless white solid.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue was partitioned between tert-butyl methyl ether
  3. extractionAfter extraction with three portions of tert-butyl methyl ether the combined organic layers
  4. dry with materialwere dried over sodium sulfate
  5. concentrationconcentrated in vacuo to 0.890 g (99.5%) of the title compound as a colorless white solid

Sources & evidence

ORD record
ord-8d73113be6b546efb0e57e531c85645e
Source dataset
uspto-grants-2011_01
Patent number
US07872022B2

Reaction notes

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