Sodium hydride → HCID 20244760, compound

HRID 647856Notes

Reaction equation

HRID 647856 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])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 13243514HCID 13243514, compound

Product 1

HCID 20244760HCID 20244760, 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 (4.0 g) in dry dimethylformamide was added under a nitrogen atmosphere to a stirred suspension of sodium hydride [from the 60% mineral oil dispersion (0.42 g) washed with petroleum ether (3×80 ml)] in dry dimethylformamide (100 ml) at room temperature to which tetrabutylammonium bromide (3.1 g) had been added. Stirring was continued for an additional 30 minutes at room temperature, when a solution of benzyl bromoacetate (2.2 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 magnesium sulfate, 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 (1:1; 600 ml) gave an oil, characterized as isomer A of the title compound; NMR (CDCl3) 5.12 (s, 4H), 4.50 (q, 2H). Elution with an additional 2 liters of the solvent mixture gave an oil characterized as isomer B of the title compound; NMR(CDCl3)δ 5.17(s, 2H), 5.03 (d, 2H), 4.60 (q, 2H).

Workup

  1. washwashed with petroleum ether (3×80 ml)] in dry dimethylformamide (100 ml) at room temperature to which tetrabutylammonium bromide (3.1 g)
  2. additionhad been added
  3. additionwhen a solution of benzyl bromoacetate (2.2 g) in dry dimethylformamide (10 ml) was added
  4. waitAfter an additional 30 minutes at room temperature
  5. temperaturethe reaction mixture was heated to 50°
  6. temperaturemaintained at that temperature for 18 hours
  7. customthe solvent removed under high vacuum
  8. additionWater (150 ml) was added
  9. extractionthe solution extracted with ethyl acetate (2×300 ml)
  10. washThe combined ethyl acetate solutions were washed with water (100 ml)
  11. dry with materialdried over magnesium sulfate
  12. customthe solvent removed under reduced pressure
  13. customto give a brown oil which
  14. customwas chromatographed on silica gel (250 g)
  15. washElution with toluene/ethyl acetate (1:1; 600 ml)
  16. customgave an oil

Sources & evidence

ORD record
ord-08c342b8ffae47eba9a75a5475db24b8
Source dataset
uspto-grants-1983_10
Patent number
US04410520

Reaction notes

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