Acetonitrile → 1-ethoxycarbonylmethyl-3-[(2-oxo-(3S)-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)-amino]-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one

HRID 745744Notes

Reaction equation

HRID 745744 reaction equation
Br[CH:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[N:4]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:3]1=[O:19].N[C@H:21]1[CH2:28][CH2:27][CH2:26][NH:25][C:23](=[O:24])[CH2:22]1.C(#[N:31])C>>[CH2:17]([O:16][C:14]([CH2:13][N:4]1[C:5]2[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=2[CH2:7][CH2:8][CH:2]([NH:31][C@H:22]2[CH2:21][CH2:28][CH2:27][CH2:26][NH:25][C:23]2=[O:24])[C:3]1=[O:19])=[O:15])[CH3:18]

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 133399633-bromo-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-oneHCID 18603542(S)-4-Aminoazepan-2-one

Product 1

HCID 186035411-ethoxycarbonylmethyl-3-[(2-oxo-(3S)-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)-amino]-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one

Procedure

A solution of 15.3 g of 3-bromo-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one and 30 g of 3-(S)-amino-ε-caprolactam [L-(-)-3-aminocaprolactam] in 400 ml of acetonitrile is heated under reflux for 48 hours. The reaction mixture is cooled to room temperature, filtered, and the filtrate is evaporated to dryness. The residue is dissolved in 200 ml methylene chloride, the methylene chloride solution is washed with 2×200 ml of water and then extracted with 2×100 ml of 2N hydrochloric acid. The acidic extract is neutralized to pH 8 by addition of solid potassium carbonate. Extraction with methylene chloride yields 1-ethoxycarbonylmethyl-3-[(2-oxo-(3S)-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)-amino]-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one as a mixture of diastereoisomers. The crude product is recrystallized from methanol to yield 1-ethoxycarbonylmethyl-3-[(2-oxo-(3S)-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)-amino]-2,3,4,5-tetrahydro-1H-1-(3S)-benzazepin-2-one, m.p. 148°- 150°, the compound of formula IIa wherein COR represents carboxy.

Workup

  1. temperatureunder reflux for 48 hours
  2. filtrationfiltered
  3. customthe filtrate is evaporated to dryness
  4. dissolutionThe residue is dissolved in 200 ml methylene chloride
  5. washthe methylene chloride solution is washed with 2×200 ml of water
  6. extractionextracted with 2×100 ml of 2N hydrochloric acid
  7. extractionThe acidic extract
  8. additionis neutralized to pH 8 by addition of solid potassium carbonate
  9. extractionExtraction with methylene chloride

Sources & evidence

ORD record
ord-e17007759ec74ca7bcb70c4247d22200
Source dataset
uspto-grants-1986_07
Patent number
US04600534

Reaction notes

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