Acetic Acid → Ethyl 10-(benzyl(methyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

HRID 1093081Notes

Reaction equation

HRID 1093081 reaction equation
Cl.[NH2:2][C:3]12[CH2:11][CH2:10][CH:7]([CH2:8][CH2:9]1)[CH2:6][N:5]1[C:12](=[O:30])[C:13]([O:21][C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:23])=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:15]=[C:4]21.[CH2:31](N(CC)CC)C.[CH:38](=O)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.CC(O)=O.[BH3-]C#N.[Na+].C=O>ClCCCl>[CH2:38]([N:2]([CH3:31])[C:3]12[CH2:11][CH2:10][CH:7]([CH2:8][CH2:9]1)[CH2:6][N:5]1[C:12](=[O:30])[C:13]([O:21][C:22]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[O:23])=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:15]=[C:4]21)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 66588778Ethyl 10-amino-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate hydrochloride

Product 1

HCID 57905222Ethyl 10-(benzyl(methyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of ethyl 10-amino-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate hydrochloride (12.75 g, 29.4 mmol) in 1,2-dichloroethane (500 mL) was added triethylamine (4.10 mL, 29.4 mmol) and the resulting mixture was stirred for 5 min. Benzaldehyde (5.94 mL, 58.8 mmol), AcOH (1.682 mL, 29.4 mmol) and NaCNBH3 (5.54 g, 88 mmol) were then added and the mixture stirred at room temp for 6 h. Formaldehyde (4.38 mL, 58.8 mmol) was then added to the reaction and the mixture was stirred at room temperature for 16 h. The reaction was quenched with sat. NaHCO3 and extracted with dichloromethane, dried (Na2SO4), filtered and concentrated. The crude product was the recrystallized from ethyl acetate to afford the title compound (11.6 g, 23.13 mmol, 79% yield)as an off-white solid. 1H NMR (500 MHz, CDCl3) δ: 8.20 (2 H, d, J=7.32 Hz), 7.63 (1 H, t, J=7.32 Hz), 7.50 (2 H, t, J=7.78 Hz), 7.39 (2 H, d, J=7.63 Hz), 7.31 (2 H, t, J=7.48 Hz), 7.20-7.23 (1 H, m), 4.28-4.34 (2 H, m), 4.09 (4 H, brs), 2.53 (3 H, s), 2.47 (1 H, brs), 2.32-2.42 (2 H, m), 2.02-2.10 (2 H, m), 1.89-1.99 (2 H, m), 1.66-1.74 (2 H, m), 1.22 (3 H, t, J=7.17 Hz). LCMS (M+H)=502.37.

Workup

  1. stirringthe mixture stirred at room temp for 6 h
  2. stirringthe mixture was stirred at room temperature for 16 h
  3. customThe reaction was quenched with sat. NaHCO3
  4. extractionextracted with dichloromethane
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-7ff541fa0d32478e82b854db63b2d086
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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