Tetrahydrofuran → tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

HRID 43600Notes

Reaction equation

HRID 43600 reaction equation
C1COCC1.[NH2:6][C@H:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][C@H:8]1[O:20][CH3:21].C(=O)(O)[O-].[Na+].Cl[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>O>[CH2:31]([O:30][C:28]([NH:6][C@H:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:9][C@H:8]1[O:20][CH3:21])=[O:29])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 57362389(3R,4S)-4-Amino-1-boc-3-methoxypiperidine

Product 1

HCID 86648489tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

THF (20 mL) and water (15 mL) were added to tert-butyl cis(±)-4-amino-3-methoxypiperidine-1-carboxylate (described in Example (1e), 4.6 g, 20 mmol). The mixture was stirred, during which sodium bicarbonate (3.44 g, 40 mmol) and benzyl chloroformate (3.95 g, 22 mmol) were added at room temperature, followed by stirring for one hour. The reaction solution was diluted with water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 1/2, 1/1) to obtain 6.89 g of the title compound as a colorless solid (95%).

Workup

  1. additionwere added at room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 1/2, 1/1)

Sources & evidence

ORD record
ord-da22337b9bd14591aeccc26c79005c28
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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