Glycyl chloride--hydrogen chloride (1/1) → 7-Chloro-1-(2,3-dihydroxypropyl)-5-(o-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

HRID 1658438Notes

Reaction equation

HRID 1658438 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:17][CH2:18][CH:19]2[CH2:23][O:22]C(C)(C)[O:20]2)=[C:6]([CH:16]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])=O.Cl.[NH2:27][CH2:28][C:29](Cl)=[O:30]>C(Cl)(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:17]([CH2:18][CH:19]([OH:20])[CH2:23][OH:22])[C:29](=[O:30])[CH2:28][N:27]=[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[F:15])[C:6]=2[CH:16]=1

Participants

4

Reactant 2

HCID 15561435Glycyl chloride--hydrogen chloride (1/1)HCID 21529392HCID 21529392, compound

Product 1

HCID 30504337-Chloro-1-(2,3-dihydroxypropyl)-5-(o-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
25 °C

Procedure

1 g of 5-chloro-2-{[(2,2-dimethyl-1,3-dioxolan-4-yl)-methyl]-amino}-2'-fluorobenzophenone are dissolved in 25 ml of absolute carbon tetrachloride, treated with 1.5 g of glycyl chloride hydrochloride and stirred for 1 hour at 25°C. Then the solvent is completely distilled off on a rotary evaporator and the residue is stirred with 25 ml of 3 N hydrochloric acid for 30 minutes. Subsequently the aqueous acidic solution is extracted with ether, made alkaline with 3 N sodium hydroxide or ammonia and extracted with ethyl acetate. The ethyl acetate phase is washed with water, dried over magnesium sulfate, filtered and evaporated. By chromatography on silica gel with ethyl acetate/methanol (9:1) there is isolated from the residue pure 7-chloro-1-(2,3-dihydroxypropyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one of melting point 116°-117°C. The compounds resulting as intermediates in the reaction 2-amino-4'-chloro-N-[(2,2-dimethyl-1,3-dioxolan-4-yl)-methyl]-2' -(2-fluorobenzoyl)-acetanilide and 2-amino-4'-chloro-N-(2,3-dihydroxypropyl)-2'-(2-fluorobenzoyl)-acetanilide are not isolated.

Workup

  1. distillationThen the solvent is completely distilled off on a rotary evaporator
  2. stirringthe residue is stirred with 25 ml of 3 N hydrochloric acid for 30 minutes
  3. extractionSubsequently the aqueous acidic solution is extracted with ether
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate phase is washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-bda0b2b04098430cbc9d964c12e15dd0
Source dataset
uspto-grants-1976_06
Patent number
US03963777

Reaction notes

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