Sodium borohydride → tert-butyl (3R,4S)-3-fluoro-4-hydroxypiperidine-1-carboxylate

HRID 1468002Notes

Reaction equation

HRID 1468002 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([F:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[F:15][C@H:10]1[C@@H:11]([OH:14])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]1.[F:15][C@H:10]1[C@H:11]([OH:14])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 10560711TERT-BUTYL 3-FLUORO-4-OXOPIPERIDINE-1-CARBOXYLATE

Product 2

HCID 40152150rac-tert-butyl (3R,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylateYield 24%HCID 40152152tert-butyl (3R,4S)-3-fluoro-4-hydroxypiperidine-1-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of tert-butyl-3-fluoro-4-oxopiperidine-1-carboxylate (1.3 g, 6.0 mmol) in methanol (15 mL), NaBH4 (0.29 g, 7.7 mmol) was added at 0° C. and stirred for 2-3 h. Methanol was removed in vacuo and the residue was diluted with ethyl acetate and washed with water. The organic layer was separated, concentrated in vacuo and the residue was purified by flash column chromatography to give cis(±)-tert-butyl 3-fluoro-4-hydroxypiperidine-1-carboxylate (0.850 g, 65%) and trans(±)-tert-butyl 3-fluoro-4-hydroxypiperidine-1-carboxylate (0.315 g, 24%); MS: 242.1 (M+23).

Workup

  1. customMethanol was removed in vacuo
  2. additionthe residue was diluted with ethyl acetate
  3. washwashed with water
  4. customThe organic layer was separated
  5. concentrationconcentrated in vacuo
  6. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-5314ba8e45cb45899f242d5e463336fd
Source dataset
uspto-grants-2015_04
Patent number
US09000175B2

Reaction notes

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