Tetrahydrofuran → Tert-butyl 4-(4-{[(benzyloxy)carbonyl]amino}-2-methoxyphenyl)piperidine-1-carboxylate

HRID 869252Notes

Reaction equation

HRID 869252 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[C:4]([O:21][CH3:22])[CH:3]=1.C1COCC1.C(=O)([O-])O.[Na+].Cl[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35]>C(OCC)(=O)C.O>[CH2:37]([O:36][C:34]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:10][CH2:9]2)=[C:4]([O:21][CH3:22])[CH:3]=1)=[O:35])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 66642900Tert-butyl 4-(4-amino-2-methoxyphenyl)piperidine-1-carboxylate

Product 1

HCID 66642793Tert-butyl 4-(4-{[(benzyloxy)carbonyl]amino}-2-methoxyphenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of tert-butyl 4-(4-amino-2-methoxy-phenyl)piperidine-1-carboxylate (Preparation Example 413) (4.25 g) and THF (100 mL), sodium hydrogen carbonate (1.28 g) and water (30 mL) were added, followed by dropwise addition of benzyl chloroformate (1.98 mL) under ice cooling and stirring overnight. After addition of water and extraction with ethyl acetate, the extract was washed with saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=2:1) to give tert-butyl 4-(4-{[(benzyloxy)carbonyl]amino}-2-methoxyphenyl)piperidine-1-carboxylate (4.92 g) as a colorless amorphous.

Workup

  1. additionwere added
  2. washthe extract was washed with saturated aqueous sodium chloride
  3. dry with materialAfter drying over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off
  5. customthe residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-1a466f8d8a674e789d2193fc5ee87527
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

Loading…