Sodium hydride → (3RS)-1-(benzofuran-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one

HRID 963478Notes

Reaction equation

HRID 963478 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[NH:14][C:13](=[O:21])[CH:12]([N:22]2[C:26](=[O:27])[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3[C:23]2=[O:32])[N:11]=1.Br[CH2:34][C:35]1[O:36][C:37]2[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=2[CH:39]=1>CN(C)C=O>[O:36]1[C:37]2[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=2[CH:39]=[C:35]1[CH2:34][N:14]1[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[F:3])=[N:11][CH:12]([N:22]2[C:23](=[O:32])[C:24]3=[CH:31][CH:30]=[CH:29][CH:28]=[C:25]3[C:26]2=[O:27])[C:13]1=[O:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 123263162-(Bromomethyl)-1-benzofuranHCID 19081136(3RS)-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one

Product 1

HCID 19081303(3RS)-1-(benzofuran-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-oneYield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (0.185 g of a 60% dispersion in mineral oil) in dry N,N-dimethylformamide (5 ml) was added (3RS)-2,3-dihydro-5-(2-fluorophenyl)-3-phtalimido-1H-1,4-benzodiazepin-2-one (1.700 g) under stirring at cooling in an ice-bath. The mixture was stirred under the same condition for 1 hour and then at room temperature for 1.5 hours. To the mixture was added dropwise a solution of 2-bromomethylbenzofuran (1.076 g) in N,N-dimethylformamide (5 ml) under cooling in an ice-bath. After completion of the addition, the mixture was allowed to stand to room temperature overnight. The reaction mixture was concentrated in vacuo. The residue was treated with ethyl acetate and water. The organic layer was washed with water and a brine, and dried over magnesium sulfate. Removal of the solvent gave (3RS)-1-(benzofuran-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one (1.018 g) which was used in a following reaction step without further purification.

Workup

  1. temperatureat cooling in an ice-bath
  2. stirringThe mixture was stirred under the same condition for 1 hour
  3. temperatureunder cooling in an ice-bath
  4. additionAfter completion of the addition
  5. waitto stand to room temperature overnight
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. additionThe residue was treated with ethyl acetate and water
  8. washThe organic layer was washed with water
  9. dry with materiala brine, and dried over magnesium sulfate
  10. customRemoval of the solvent

Sources & evidence

ORD record
ord-c4bbb3f9153c4a9fab39696a764f2a31
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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