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 489867Notes

Reaction equation

HRID 489867 reaction equation
C(C=CC(OCC)=O)(=O)C1C=CC=CC=1.N[C@H]1CCC2C=CC=CC=2N(CC(OC(C)(C)C)=O)C1=O.[C:37]([O:41][C:42](=[O:69])[CH2:43][N:44]1[C:50](=[O:51])[CH:49]([NH:52][CH:53]2[CH2:57][CH:56]([C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)[O:55][C:54]2=[O:64])[CH2:48][CH2:47][C:46]2[CH:65]=[CH:66][CH:67]=[CH:68][C:45]1=2)([CH3:40])([CH3:39])[CH3:38].C([O-])=O.[NH4+]>C1(C)C=CC=CC=1.[Pd]>[C:54]([CH:53]([NH:52][CH:49]1[CH2:48][CH2:47][C:46]2[CH:65]=[CH:66][CH:67]=[CH:68][C:45]=2[N:44]([CH2:43][C:42]([O:41][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:69])[C:50]1=[O:51])[CH2:57][CH2:56][C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1)([OH:64])=[O:55]

Participants

7

Reactant 4

HCID 5698852-Butenoic acid, 4-oxo-4-phenyl-, ethyl esterHCID 2723923Ammonium formateHCID 63506241,1-Dimethylethyl ((3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetateHCID 85122760[2-Oxo-3-(2-oxo-5-phenyl-tetrahydro-furan-3-ylamino)-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl]-acetic acid tert-butyl ester

Product 1

HCID 222629803-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-oneYield 54%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

Ethyl 3-benzoylacrylate (13a) (55.6 g, 272 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, 228 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. After completion of the reaction the catalyst is filtered off through Celite, 100 ml of acetic acid are added and the solvent mixture is reacted at 20–30° C. for 18 h. After lactonization to compound (17), ammonium formate (51.4 g, 816 mmoles) and 10% Pd—C (26 g, 22 mmoles) are added. The reaction mixture is heated to 40° C. for 3 h, after that the catalyst is filtered off through Celite and solvents are evaporated off. The residue is taken up with acetone (600 ml) and acetic acid (200 ml), heated to dissolution and cooled. The resulting precipitate is filtered, washed with 80 ml of acetone1 and dried to give 3-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (15) (60.7 g, yield: 54%).

Workup

  1. waitThe resulting mixture is left
  2. customAfter completion of the reaction the catalyst
  3. filtrationis filtered off through Celite, 100 ml of acetic acid
  4. additionare added
  5. customthe solvent mixture is reacted at 20–30° C. for 18 h
  6. filtrationafter that the catalyst is filtered off through Celite and solvents
  7. customare evaporated off
  8. temperatureheated to dissolution
  9. temperaturecooled
  10. filtrationThe resulting precipitate is filtered
  11. washwashed with 80 ml of acetone1
  12. customdried

Sources & evidence

ORD record
ord-34541844536640358c03cffc6b8302b5
Source dataset
uspto-grants-2005_12
Patent number
US06979736B2

Reaction notes

Loading…