tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-[(2-ethoxy-2-oxoethyl)amino]piperidine-1-carboxylate

HRID 550389Notes

Reaction equation

HRID 550389 reaction equation
C([BH3-])#N.[Na+].[C:5]([N:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1)([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].Cl.[CH2:20]([O:22][C:23](=[O:26])[CH2:24][NH2:25])[CH3:21]>CO>[CH2:20]([O:22][C:23](=[O:26])[CH2:24][NH:25][CH:15]1[CH2:16][CH2:17][N:12]([C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])[CH2:13][CH2:14]1)[CH3:21]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2723640Glycine ethyl ester, hydrochlorideHCID 5003444Sodium cyanoborohydride

Product 1

HCID 15380724Tert-butyl 4-[(2-ethoxy-2-oxoethyl)amino]piperidine-1-carboxylateYield 83.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium cyanoborohydride (189 mg, 3.01 mmol) was added to a solution of 1-boc-4-piperidone (500 mg, 2.51 mmol) and glycine ethyl ester hydrochloride (350 mg, 2.51 mmol) in methanol (12.5 mL). After 16 h, the mixture was quenched with saturated ammonium chloride solution, concentrated, and partitioned between dichloromethane and saturated sodium bicarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)] gave the title compound (600 mg).

Workup

  1. customthe mixture was quenched with saturated ammonium chloride solution
  2. concentrationconcentrated
  3. custompartitioned between dichloromethane and saturated sodium bicarbonate solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)]

Sources & evidence

ORD record
ord-e9738eed29e54545ac7c85e18e816c0e
Source dataset
uspto-grants-2011_05
Patent number
US07947678B2

Reaction notes

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