Sodium hydride → HCID 20244767, compound

HRID 647869Notes

Reaction equation

HRID 647869 reaction equation
[CH2:1]([O:8][C:9]([CH:11]([NH:20][CH:21]1[CH2:27][CH2:26][C:25]2[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=2[NH:23][C:22]1=[O:32])[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>CN(C)C=O>[CH2:1]([O:8][C:9]([CH2:11][N:23]1[C:24]2[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=2[CH2:26][CH2:27][CH:21]([NH:20][CH:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:22]1=[O:32])=[O:10])[CH3:2]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 13243514HCID 13243514, compound

Product 1

HCID 20244767HCID 20244767, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(1-benzyloxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]-benzazepin-2-one (5.0 g) in dry dimethylformamide was added under a nitrogen atmosphere to a stirred suspension of sodium hydride [from the 60% mineral oil dispersion (0.5 g) washed with petroleum ether (3×80 ml)] in dry dimethylformamide (100 ml) at room temperature. Stirring was continued for an additional 30 minutes at room temperature, when a solution of ethyl bromoacetate (2.0 g) in dry dimethylformamide (10 ml) was added. After an additional 30 minutes at room temperature the reaction mixture was heated to 50°, and maintained at that temperature for 18 hours. The reaction mixture was cooled to room temperature and the solvent removed under high vacuum. Water (150 ml) was added and the solution extracted with ethyl acetate (2×300 ml). The combined ethyl acetate solutions were washed with water (100 ml), dried over MgSO4, and the solvent removed under reduced pressure to give a brown oil which was chromatographed on silica gel (250 g). Elution with toluene/ethyl acetate (9:1; 600 ml) gave an oil, characterized as isomer A of the title compound. Elution with an additional 1000 ml of the solvent mixture gave an oil characterized as isomer B of the title compound.

Workup

  1. washwashed with petroleum ether (3×80 ml)] in dry dimethylformamide (100 ml) at room temperature
  2. additionwhen a solution of ethyl bromoacetate (2.0 g) in dry dimethylformamide (10 ml) was added
  3. temperaturemaintained at that temperature for 18 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customthe solvent removed under high vacuum
  6. additionWater (150 ml) was added
  7. extractionthe solution extracted with ethyl acetate (2×300 ml)
  8. washThe combined ethyl acetate solutions were washed with water (100 ml)
  9. dry with materialdried over MgSO4
  10. customthe solvent removed under reduced pressure
  11. customto give a brown oil which
  12. customwas chromatographed on silica gel (250 g)
  13. washElution with toluene/ethyl acetate (9:1; 600 ml)
  14. customgave an oil

Sources & evidence

ORD record
ord-bb9e664fa7664437bb83dff129c22699
Source dataset
uspto-grants-1983_10
Patent number
US04410520

Reaction notes

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