tert-Butyl 4-oxopiperidine-1-carboxylate → 1,1-Dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylate

HRID 80462Notes

Reaction equation

HRID 80462 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].O=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CC(O)=O.CCOC(C)=O>[CH2:13]([O:12][C:9]1[CH:10]=[CH:11][C:2]([NH:1][CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)=[C:3]([C:4]([O:6][CH3:7])=[O:5])[CH:8]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 11288356Methyl 2-amino-5-(benzyloxy)benzoate2×

Product 1

HCID 595872031,1-Dimethylethyl 4-{[4-(benzyloxy)-2-(methoxycarbonyl)phenyl]amino}piperidine-1-carboxylateYield 297.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2 g of methyl 2-amino-5-(benzyloxy)benzoate, 3.1 g of 1,1-dimethylethyl 4-oxopiperidine-1-carboxylate and 3.29 g of NaBH(OAc)3 in 10 ml of AcOH is irradiated under a microwave field (Biotage Initiator Sixty) at 110° C. for 20 min. The same reaction is repeated with two other lots of 2 g of methyl 2-amino-5-(benzyloxy)benzoate. The three reaction media are combined. The combined product is taken up in AcOEt. The organic phase is washed with water, with a saturated NH4Cl solution and with a saturated NaHCO3 solution, dried over Na2SO4 and filtered, and the solvent is evaporated under reduced pressure. The residue is chromatographed on silica gel, elution being carried out with an AcOEt/heptane mixture, (5/95, v/v) as far as (30/70, v/v), to give 10.2 g of the expected product.

Workup

  1. customThe same reaction
  2. customThe three reaction media
  3. washThe organic phase is washed with water, with a saturated NH4Cl solution and with a saturated NaHCO3 solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent is evaporated under reduced pressure
  7. customThe residue is chromatographed on silica gel, elution

Sources & evidence

ORD record
ord-421611c81f5a4ed9b5ad8b4d287bceb7
Source dataset
uspto-grants-2014_09
Patent number
US08846654B2

Reaction notes

Loading…