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

HRID 1022867Notes

Reaction equation

HRID 1022867 reaction equation
[BH4-].[Na+].[C:3]([N:10]1[CH2:15][CH2:14][C:13](=[O:16])[CH2:12][CH:11]1[CH3:17])([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4]>CCO>[C:3]([N:10]1[CH2:15][CH2:14][C@@H:13]([OH:16])[CH2:12][C@@H:11]1[CH3:17])([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4]

Participants

4

Reactant 2

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

Product 1

HCID 450974411-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4R)-(9CI)

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

213 mg (5.6 mmol) of NaBH4 were added portionwise at 0° C. to a solution of 1.0 g (4.7 mmol) 1-Boc-2-methyl-piperidin-4-on in 10 mL EtOH. The mixture was stirred at room temperature for another 2 h. The solvent was removed by distillation and the remainder was dissolved in water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetated and the combined organic layers were dried over Na2SO4. After filtration the solvent was removed by distillation and the crude product was purified by column chromatography n-heptane/ethyl acetate (1/1) to yield 367 mg (36%) of the cis-isomer 25 and 205 mg (20%) of the trans-isomer 26 in addition to 97 mg (10%) mixture of both isomers.

Workup

  1. customThe solvent was removed by distillation
  2. dissolutionthe remainder was dissolved in water
  3. extractionThe aqueous layer was extracted twice with ethyl
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationAfter filtration the solvent
  6. customwas removed by distillation
  7. customthe crude product was purified by column chromatography n-heptane/ethyl acetate (1/1)
  8. customto yield 367 mg (36%) of the cis-isomer 25 and 205 mg (20%) of the trans-isomer 26

Sources & evidence

ORD record
ord-f0b16671052b4f259bdaae732bc75401
Source dataset
uspto-grants-2014_05
Patent number
US08722671B2

Reaction notes

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