2-Butenoic acid, 4-oxo-4-phenyl-, ethyl ester → 3-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one

HRID 489863Notes

Reaction equation

HRID 489863 reaction equation
[C:1]([CH:9]=[CH:10][C:11]([O:13]CC)=[O:12])(=O)[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].[BH4-].[Na+].C([O-])=O.[NH4+]>C1(C)C=CC=CC=1.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+].[Pd]>[C:11]([CH:10]([NH:16][CH: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]([CH3:34])([CH3:33])[CH3:35])=[O:30])[C:18]1=[O:36])[CH2:9][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([OH:13])=[O:12]

Participants

9

Reactant 4

HCID 5698852-Butenoic acid, 4-oxo-4-phenyl-, ethyl esterHCID 2723923Ammonium formateHCID 4311764Sodium borohydrideHCID 63506241,1-Dimethylethyl ((3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetate

Product 1

HCID 222629803-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-oneYield 52.2%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 70681Tetrabutylammonium ChlorideCatalystHCID 1140TolueneSolventHCID 14798Sodium HydroxideSolvent

Procedure

Ethyl 3-benzoylacrylate (13a) (55.6 g, 272 mmoles) is drooped into a solution of (3S)-3-amino-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (11) (66.2 g, 228 mmoles) in 200 ml of toluene, at room temperature in 1 h. The resulting mixture is left under stirring for 18 h, then a solution of sodium borohydride (228 mmoles 8.6 g) and tetrabutylammonium chloride (5.0 g) in 50 ml of 0.1 M NaOH is added and the mixture is stirred at room temperature for 18 h. The aqueous phase is separated, 50 ml of acetic acid are added to the organic phase and the mixture is left under stirring for 30′, then added with 10% Pd—C (26 g, 22 mmoles) and ammonium formate (456 mmoles, 33.3 g) and left under stirring for 4 h. Afterwards, the catalyst is filtered off through Celite and 100 ml of water is added. The resulting precipitate is filtered, washed with 20 ml of isopropanol and dried to give 3-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (15) (53.9 g, yield: 48%).

Workup

  1. waitThe resulting mixture is left
  2. stirringthe mixture is stirred at room temperature for 18 h
  3. customThe aqueous phase is separated
  4. addition50 ml of acetic acid are added to the organic phase
  5. waitthe mixture is left
  6. stirringunder stirring for 30′,
  7. waitleft
  8. stirringunder stirring for 4 h
  9. filtrationAfterwards, the catalyst is filtered off through Celite and 100 ml of water
  10. additionis added
  11. filtrationThe resulting precipitate is filtered
  12. washwashed with 20 ml of isopropanol
  13. customdried

Sources & evidence

ORD record
ord-ea9f74cff65842d7b2d5342fe0badcd9
Source dataset
uspto-grants-2005_12
Patent number
US06979736B2

Reaction notes

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