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

HRID 1926647Notes

Reaction equation

HRID 1926647 reaction equation
[F:1][CH:2]1[C:7](=[O:8])[CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1.[BH4-].[Na+]>CO>[F:1][C@H:2]1[C@@H:7]([OH:8])[CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1.[F:1][C@H:2]1[C@H:7]([OH:8])[CH2:6][CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 42609253Benzyl 3-fluoro-4-oxopiperidine-1-carboxylate

Product 2

HCID 52324487(3R,4S)-Benzyl 3-fluoro-4-hydroxypiperidine-1-carboxylateHCID 52324488benzyl (3R,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of benzyl 3-fluoro-4-oxopiperidine-1-carboxylate (200 g, 0.797 mol) in methanol (1 L) was added NaBH4 (24.4 g, 0.636 mol) in portions at 0° C. After the addition, the mixture was stirred for 4 h and then quenched with water (200 mL). The mixture was concentrated, and then ethyl acetate and water were added to the residue. The organic layer was separated, dried over sodium sulfate and concentrated. The residue was purified via column chromatography (EtOAc/petroleum ether=1:6) to afford benzyl cis-3-fluoro-4-hydroxypiperidine-1-carboxylate and benzyl trans-3-fluoro-4-hydroxypiperidine-1-carboxylate. 1H NMR (600 MHz, CDCl3-D6) 7.50-7.30 (m, 5H); 5.13 (s, 2H); 4.70-4.50 (d, 1H); 4.10-3.70 (m, 3H); 3.48 (s, 1H); 3.23 (s, 1H); 2.50 (s, 1H); 1.90-1.70 (m, 2H).

Workup

  1. additionAfter the addition
  2. customquenched with water (200 mL)
  3. concentrationThe mixture was concentrated
  4. additionethyl acetate and water were added to the residue
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified via column chromatography (EtOAc/petroleum ether=1:6)

Sources & evidence

ORD record
ord-06906f155cc547438fe06c433ebaaaf6
Source dataset
uspto-grants-2012_05
Patent number
US08183245B2

Reaction notes

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