Sodium borohydride → 1-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4S)-(9CI)

HRID 1051747Notes

Reaction equation

HRID 1051747 reaction equation
[BH4-].[Na+].[CH3:3][CH:4]1[CH2:9][C:8](=[O:10])[CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]>C(O)C>[OH:10][C@H:8]1[CH2:7][CH2:6][N:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@@H:4]([CH3:3])[CH2:9]1.[OH:10][C@@H:8]1[CH2:7][CH2:6][N:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@@H:4]([CH3:3])[CH2:9]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 12992764tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylate

Product 2

HCID 450974401-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4S)-(9CI)Yield 36%HCID 450974411-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4R)-(9CI)Yield 20%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Following the procedure found in Plettenburg, Oliver et. Al (PCT Int. Appl., 2007012421), sodium borohydride (213 mg, 5.6 mmol) was added portion-wise to a solution of tert-butyl 2-methyl-4-oxopiperidine-1-carboxylate (1.0 g, 4.7 mmol) in ethanol (10 mL). The mixture was stirred at room temperature for 2 h. The solution was concentrated in vacuo and then partitioned between water (40 mL) and ethyl acetate (40 mL). The aqueous layer was extracted twice with ethyl acetate (40 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via column chromatography on silica gel (Biotage 50 g column, gradient elution with 40-50% ethyl acetate in hexanes) to afford (rac)-tert-butyl (cis)-4-hydroxy-2-methylpiperidine-1-carboxylate (367 mg, 36%) and (rac)-tert-butyl (trans)-4-hydroxy-2-methylpiperidine-1-carboxylate (205 mg, 20%) as white solids.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. custompartitioned between water (40 mL) and ethyl acetate (40 mL)
  3. extractionThe aqueous layer was extracted twice with ethyl acetate (40 mL)
  4. washThe combined organic layers were washed with brine (20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via column chromatography on silica gel (Biotage 50 g column, gradient elution with 40-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bd77bf5511e34bcd9e43fc4f71453bb7
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

Loading…