Ammonia → 4-Amino-1-Boc-piperidine

HRID 1642240Notes

Reaction equation

HRID 1642240 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH3:15].[BH4-].[Na+]>CCO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:15])[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 4311764Sodium borohydrideHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylate

Product 1

HCID 12682914-Amino-1-Boc-piperidineYield 44%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

A mixture of 1-BOC-piperidone (2 g, 10 mmol), titanium(IV) isopropoxide and ammonia in EtOH was stirred under argon in a capped flask at room temperature for 6 h. Sodium borohydride was then added and the resulting mixture was stirred at room temperature for an additional 3 h. The reaction was then quenched by pouring it into ammonium hydroxide (2M, 25 mL). The resulting inorganic precipitate was filtered off, and washed with EtOAc (2×25 mL). The organic layer was separated and the remaining aqueous layer was extracted with EtOAc (2×25 mL). The combined organic fractions were next extracted with HCl (1M, 30 mL) to separate the neutral materials. The acidic extracts were washed with EtOAc (50 mL), then treated with aqueous NaOH 2M to pH 10-12, and extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo to afford 4-aminopiperidine-1-carboxylic acid tert-butyl ester as a white solid (882 mg, 44%) which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 1.12-1.27 (3H, m), 1.42 (9H, s, 3CH3), 1.97 (2H, m), 1.73 (2H, m), 2.76 (3H, m) and 4.01 (2H, m).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for an additional 3 h
  2. customThe reaction was then quenched
  3. additionby pouring it into ammonium hydroxide (2M, 25 mL)
  4. filtrationThe resulting inorganic precipitate was filtered off
  5. washwashed with EtOAc (2×25 mL)
  6. customThe organic layer was separated
  7. extractionthe remaining aqueous layer was extracted with EtOAc (2×25 mL)
  8. extractionThe combined organic fractions were next extracted with HCl (1M, 30 mL)
  9. customto separate the neutral materials
  10. washThe acidic extracts were washed with EtOAc (50 mL)
  11. additiontreated with aqueous NaOH 2M to pH 10-12
  12. extractionextracted with EtOAc (3×50 mL)
  13. washThe combined organic extracts were washed with brine
  14. dry with materialdried (MgSO4)
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dc748b045ac04d6b8c6a6698b226ddd5
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

Loading…