Water → OPC 51803

HRID 1870260Notes

Reaction equation

HRID 1870260 reaction equation
[C:1]([CH2:4][C@@H:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]([C:16](=[O:29])[C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:19][C:18]=2[Cl:28])[CH2:8][CH2:7][CH2:6]1)([OH:3])=O.[CH:30]([NH2:33])([CH3:32])[CH3:31].P(C#N)(OCC)(OCC)=O.O>CN(C)C=O.C(OCC)(=O)C.CCCCCC>[CH:30]([NH:33][C:1]([CH2:4][C@@H:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]([C:16](=[O:29])[C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:19][C:18]=2[Cl:28])[CH2:8][CH2:7][CH2:6]1)=[O:3])([CH3:32])[CH3:31]

Participants

7

Reactant 4

HCID 962WaterHCID 6363IsopropylamineHCID 76257Diethyl cyanophosphonateHCID 11058732HCID 11058732, compound

Product 1

HCID 3038506OPC 51803

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of (5R)-5-carboxymethyl-1-[4-(1-pyrrolidinyl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (21 g) in dimethylformamide (400 ml) are added isopropylamine (21.7 ml) and diethyl cyanophosphate (10 g) at room temperature, and the mixture is stirred at room temperature for two hours. To the reaction solution are added water and ethyl acetate--n-hexane (10:1), and the mixture is extracted twice. The organic layer is washed successively with a 5% citric acid, a saturated aqueous sodium hydrogen carbonate solution, and water, and dried over anhydrous magnesium sulfate. The mixture is concentrated under reduced pressure to remove the solvent, and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol:ammonium hydroxide=1000:5:0.2→1000:15:0.5), and recrystallized from acetone--n-hexane to give (5R)-5-isopropylaminocarbonylmethyl-1-[4-(1-pyrrolidinyl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (12.5 g).

Workup

  1. extractionthe mixture is extracted twice
  2. washThe organic layer is washed successively with a 5% citric acid
  3. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and water, and dried over anhydrous magnesium sulfate
  4. concentrationThe mixture is concentrated under reduced pressure
  5. customto remove the solvent
  6. customthe resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol:ammonium hydroxide=1000:5:0.2→1000:15:0.5)
  7. customrecrystallized from acetone

Sources & evidence

ORD record
ord-2010a8ad820f4c61a580c4af3ad99e67
Source dataset
uspto-grants-2000_08
Patent number
US06096736

Reaction notes

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