(R)-Tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate → 1,1-Dimethylethyl (3R)-3-[(1S)-1-(3-chlorophenyl)-5,5-difluoro-1-hydroxyhexyl]-1-piperidinecarboxylate

HRID 2355372Notes

Reaction equation

HRID 2355372 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14](=[O:22])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:23][C:24]([F:31])([CH3:30])[CH2:25][CH2:26][CH2:27][Mg]Cl>C1COCC1>[C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C@@:14]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)([OH:22])[CH2:27][CH2:26][CH2:25][C:24]([F:31])([F:23])[CH3:30])[CH2:9]1)([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7]

Participants

4

Reactant 2

HCID 46831638(R)-Tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylateHCID 178461136HCID 178461136, compound

Product 1

HCID 671914461,1-Dimethylethyl (3R)-3-[(1S)-1-(3-chlorophenyl)-5,5-difluoro-1-hydroxyhexyl]-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R)-1-(tert-butoxycarbonyl)-3-(3-chlorobenzoyl)piperidine (100 mg, 0.33 mmol) in THF (2 mL) was cooled to −20° C. and 4,4-difluoropentylmagnesium chloride (˜0.79M in THF, 5.0 mL, 4.0 mmol) was added. The mixture was stirred for 2 h and quenched with sat'd NH4Cl. The aqueous layer was extracted with ether. The combined organic layers were washed with brine, dried over sodium sulfate and filtered. The solvent was removed on a roto-evaporator. The crude product was purified using flash chromatography (hexanes/EtOAc). N-Boc-(S)-1-(3-chlorophenyl)-5,5-difluoro-1-((R)-piperidin-3-yl)hexan-1-ol was isolated as an oil (70 mg) MS m/z 454 (M+Na).

Workup

  1. customquenched with sat'd NH4Cl
  2. extractionThe aqueous layer was extracted with ether
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was removed on a roto-evaporator
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-a728e536dfad4942978ca42b21412891
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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