Sodium hydride → HCID 20244809, compound

HRID 2418735Notes

Reaction equation

HRID 2418735 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[NH:4][C:3]1=[O:13].[H-].[Na+].Br[CH2:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19]>CN(C)C=O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:21]([O:20][C:18]([CH2:17][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][CH2:17][C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[C:3]1=[O:13])=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 62576Benzyl bromoacetateHCID 44344333-Amino-2,3,4,5-tetrahydro-1H-benzazepin-2-one

Product 1

HCID 20244809HCID 20244809, compound

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent3×

Procedure

A solution of 3-amino-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (5.0 g, 0.028 mol) in dimethylformamide (100 ml) was added under a nitrogen atmosphere to a stirred suspension of sodium hydride [prepared from the 60% mineral oil dispersion (1.2 g) by washing with petroleum ether (3×105)] in dimethylformamide (400 ml) to which tetrabutylammonium bromide (10.9 g, 0.031 mol) had been added. The reaction mixture was maintained at 50° for 15 minuites, then a solution of benzyl bromoacetate (7.2 g, 0.031 mol) in dimethylformamide (25 ml) was added. The reaction mixture was stirred for an additional 18 hours at 50°, then cooled to room temperature, and the dimethylformamide removed under high vacuum. The residue was stirred with toluene/dichloromethane (1:1, 500 ml) to precipitate inorganic salts. After filtration, the solution was evaporated under reduced pressure, and the residue chromatographed on silica gel (200 g). Elution with 0-15% ethyl acetate in toluene gave 1-benzyloxycarbonylmethyl-3-benzyloxycarbonylmethylamino-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one as the first fraction. Further elution gave 3-benzyloxycarbonylamino-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 124°-127° C. and 3-amino-1-benzyloxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (see example 1).

Workup

  1. customprepared from the 60% mineral oil dispersion (1.2 g)
  2. additionhad been added
  3. temperatureThe reaction mixture was maintained at 50° for 15 minuites
  4. customthe dimethylformamide removed under high vacuum
  5. stirringThe residue was stirred with toluene/dichloromethane (1:1, 500 ml)
  6. customto precipitate inorganic salts
  7. filtrationAfter filtration
  8. customthe solution was evaporated under reduced pressure
  9. customthe residue chromatographed on silica gel (200 g)
  10. washElution with 0-15% ethyl acetate in toluene

Sources & evidence

ORD record
ord-3dc4419cb7f24c3c803227d76386f790
Source dataset
uspto-grants-1984_09
Patent number
US04473575

Reaction notes

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