tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-hydroxypiperidine-1-carboxylate

HRID 51613Notes

Reaction equation

HRID 51613 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[BH4-].[Na+]>CO>[OH:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 4311764Sodium borohydride2×

Product 1

HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateYield 97.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of tert-butyl 4-oxo-1-piperidinecarboxylate (179.24 g, 899.62 mmol) in anhydrous methanol (1.5 L) at 0° C. under a nitrogen atmosphere was treated with sodium borohydride (34.03 g, 899.62 mmol). Sodium borohydride was added portion-wise (5 g every 10 minutes). The ice bath was removed 20 minutes after the last addition of sodium borohydride, and the reaction mixture stirred for 72 hours. To the reaction solution, 1 N sodium hydroxide aqueous solution (1 L) was added, and allowed to stir for 2 hours. The organic layer was removed under reduced pressure, and anhydrous diethyl ether (200 mL) was added. The aqueous layer was extracted with anhydrous diethyl ether (1.5 L). The organic layers were combined, washed with brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give a yellow oil. The product was further dried under high vacuum to remove residual solvent to give 177.04 g (97%) of tert-butyl 4-hydroxy-1-piperidinecarboxylate as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 4.688(s, 1H), 3.678-3.589(m, 3H), 2.940(m, 2H), 1.689-1.646(m, 2H), 1.385(s, 9H), 1.252-1.212(m, 2H).

Workup

  1. customThe ice bath was removed 20 minutes
  2. additionafter the last addition of sodium borohydride
  3. additionTo the reaction solution, 1 N sodium hydroxide aqueous solution (1 L) was added
  4. stirringto stir for 2 hours
  5. customThe organic layer was removed under reduced pressure, and anhydrous diethyl ether (200 mL)
  6. additionwas added
  7. extractionThe aqueous layer was extracted with anhydrous diethyl ether (1.5 L)
  8. washwashed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customto give a yellow oil
  13. customThe product was further dried under high vacuum
  14. customto remove residual solvent

Sources & evidence

ORD record
ord-3967bb2d344b4656bebdae5f4116adfc
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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