1,1'-Carbonyldiimidazole → ethyl 3-(1-t-butoxycarbonylmethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)2-oxo-6-phenyl-[1,3]oxazinan-4-carboxylate

HRID 489865Notes

Reaction equation

HRID 489865 reaction equation
[C:1]([CH:9]=[CH:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:16][C@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:18]1=[O:36].[C:37](N1C=CN=C1)(N1C=CN=C1)=[O:38]>C1(C)C=CC=CC=1.[Pd]>[C:32]([O:31][C:29]([CH2:28][N:19]1[C:18](=[O:36])[CH:17]([N:16]2[CH:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[O:8][C:37]2=[O:38])[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]1=2)=[O:30])([CH3:33])([CH3:35])[CH3:34]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 5698852-Butenoic acid, 4-oxo-4-phenyl-, ethyl esterHCID 63506241,1-Dimethylethyl ((3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetate

Product 1

HCID 22262974ethyl 3-(1-t-butoxycarbonylmethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)2-oxo-6-phenyl-[1,3]oxazinan-4-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 1140TolueneSolvent

Procedure

Ethyl 3-benzoylacrylate (13a) (55.6 g, 250 mmoles) is dropped into a solution of (3S)-3-amino-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (11) (66.2 g, 227 mmoles) in 200 ml of toluene, at room temperature in 1 h. The resulting mixture is left under stirring for 18 h, then added with 10% Pd—C (26 g, 22 mmoles) and hydrogenated at 3 atm for 18 h at room temperature. The catalyst is filtered off and carbonyldiimidazole (272.4 mmoles, 44.16 g) is added. After reacting for 4 h the mixture is washed 3 times with 100 ml of water. After completion of the reaction the solvent is evaporated off and the residue is purified by chromatography (eluent: hexane-ethyl acetate 7:3). A mixture of isomeric products is isolated.

Workup

  1. waitThe resulting mixture is left
  2. filtrationThe catalyst is filtered off
  3. waitAfter reacting for 4 h
  4. washthe mixture is washed 3 times with 100 ml of water
  5. customAfter completion of the reaction the solvent
  6. customis evaporated off
  7. customthe residue is purified by chromatography (eluent: hexane-ethyl acetate 7:3)
  8. additionA mixture of isomeric products
  9. customis isolated

Sources & evidence

ORD record
ord-e5a1ecd3bb7a4fb5966aae66916d79e2
Source dataset
uspto-grants-2005_12
Patent number
US06979736B2

Reaction notes

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