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 1658437Notes

Reaction equation

HRID 1658437 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:17][CH2:18][CH:19]([OH:22])[CH2:20][OH:21])=[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.[NH2:24][CH2:25][C:26](Cl)=[O:27]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:17]([CH2:18][CH:19]([OH:22])[CH2:20][OH:21])[C:26](=[O:27])[CH2:25][N:24]=[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 21529386HCID 21529386, 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 6344DichloromethaneSolvent

Procedure

3.3 g of 5-chloro-2-[(2,3-dihydroxypropyl)-amino]-2'-fluorobenzophenone are dissolved in methylene chloride and treated under anhydrous conditions with 2.6 g of glycyl chloride hydrochloride. The mixture is stirred for 2 hours at room temperature, then the methylene chloride is extensively distilled off, whereupon the residue is stirred for 30 minutes with 3 N hydrochloric acid. The acidic aqueous solution is extracted with ether, subsequently made alkaline with 3 N sodium hydroxide or concentrated ammonia and extracted with ethyl acetate. The ethyl acetate phase is washed with water, dried over magnesium sulfate, filtered and concentrated. The residue is chromatographed on silica gel with ethyl acetate, there being isolated 7-chloro-1-(2,3-dihydroxypropyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one of melting point 117°-118°C. During the aforementioned reaction, there is formed as an intermediate 2-amino-4'-chloro-N-(2,3-dihydroxypropyl)-2'-(2-fluorobenzoyl)-acetanilide, which is not isolated.

Workup

  1. distillationthe methylene chloride is extensively distilled off, whereupon the residue
  2. stirringis stirred for 30 minutes with 3 N hydrochloric acid
  3. extractionThe acidic aqueous solution is extracted with ether, subsequently made alkaline with 3 N sodium hydroxide or concentrated ammonia
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate phase is washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is chromatographed on silica gel with ethyl acetate, there

Sources & evidence

ORD record
ord-2162488fbe2944dcb768698048e34a5d
Source dataset
uspto-grants-1976_06
Patent number
US03963777

Reaction notes

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