Hydrochloric Acid → 1H-1-Benzazepine-1-acetic acid, 3-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-, hydrochloride (1:1), (3S)-rel-

HRID 482718Notes

Reaction equation

HRID 482718 reaction equation
[NH2:1][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]([OH:16])=[O:15])[C:3]1=[O:17].[CH2:18]([CH2:25][C:26](=O)[C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([BH3-])#N.[Na+].[ClH:37]>C(O)(=O)C.CO>[ClH:37].[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:1][CH:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:25][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:3]1=[O:17])([OH:16])=[O:15]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 562087Ethyl alpha-oxobenzenebutanoateHCID 5003444Sodium cyanoborohydrideHCID 13243494(3-Amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetic acid

Product 1

HCID 132435131H-1-Benzazepine-1-acetic acid, 3-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-, hydrochloride (1:1), (3S)-rel-

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

A solution of 3-amino-1-carboxymethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (10.0 g) and ethyl benzylpyruvate (26.4 g) in acetic acid (75 ml) and methanol (75 ml) was stirred at room temperature under nitrogen for 1 hour. Sodium cyanoborohydride (3.4 g) in methanol (25 ml) was added dropwise over 4 hours. The reaction mixture was stirred at room temperature for 24 hours. Concentrated hydrochloric acid (4 ml) was added dropwise, and the mixture stirred at room temperature for 1 hour. The reaction mixture was evaporated to dryness. The residue was partitioned between 150 ml of water and 50 ml of ether and adjusted to pH 9 with 40% sodium hydroxide. The layers were separated and the ether layer was discarded. The aqueous layer was adjusted to pH 4.3 with concentrated hydrochloric acid and extracted with 3×75 ml of ethyl acetate. The organic portions were dried (magnesium sulfate) and concentrated to dryness. Hydrogen chloride gas was bubbled into a solution of the crude product in 310 ml of methylene chloride for 5 minutes. The solution was evaporated and the residue was stirred in 225 ml of ether. The product was collected by filtration to give a 70:30 diastereomeric mixture as determined by high pressure liquid chromatography. The product was recrystallized from ethanol/ethyl acetate (1:3) to give 1-carboxymethyl-3-(1-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one hydrochloride melting at 246°-8° (dec.) and corresponding to the racemic isomer B.

Workup

  1. stirringthe mixture stirred at room temperature for 1 hour
  2. customThe reaction mixture was evaporated to dryness
  3. customThe residue was partitioned between 150 ml of water and 50 ml of ether
  4. customThe layers were separated
  5. extractionextracted with 3×75 ml of ethyl acetate
  6. dry with materialThe organic portions were dried (magnesium sulfate)
  7. concentrationconcentrated to dryness
  8. customHydrogen chloride gas was bubbled into a solution of the crude product in 310 ml of methylene chloride for 5 minutes
  9. customThe solution was evaporated
  10. stirringthe residue was stirred in 225 ml of ether
  11. filtrationThe product was collected by filtration
  12. customto give a 70:30 diastereomeric mixture
  13. customThe product was recrystallized from ethanol/ethyl acetate (1:3)

Sources & evidence

ORD record
ord-311d9560b93f47e0a95925494b23552d
Source dataset
uspto-grants-1986_03
Patent number
US04575503

Reaction notes

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