Chlorine → (S)-7-amino-6-chloro-5-(o-fluorophenyl)-1,3-dihydro-1,3-dimethyl-2H-1,4-benzodiazepin-2-one

HRID 1278488Notes

Reaction equation

HRID 1278488 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C@H:9]([CH3:14])[N:8]=[C:7]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[F:21])[C:6]=2[CH:22]=1.[Cl:23]Cl>>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C@H:9]([CH3:14])[N:8]=[C:7]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[F:21])[C:6]=2[C:22]=1[Cl:23]

Participants

3

Reactant 2

HCID 24526ChlorineHCID 53862516(S)-7-amino-5-(o-fluorophenyl)-1,3-dihydro-1,3-dimethyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 54545945(S)-7-amino-6-chloro-5-(o-fluorophenyl)-1,3-dihydro-1,3-dimethyl-2H-1,4-benzodiazepin-2-one

Procedure

4 g (0.011 M) of (S)-7-amino-5-(o-fluorophenyl)-1,3-dihydro-1,3-dimethyl-2H-1,4-benzodiazepin-2-one are dissolved in 35 ml of ice-cold concentrated hydrochloric acid at -10° C. and chlorine gas is conducted in at -10° C. for 1 hour. The mixture is concentrated at 0°-5° C. using a high vacuum cooling trap and a soda lime tower under a high vacuum (1-2 mmHg). The residue is made alkaline with a mixture of ice and 10% sodium bicarbonate solution. The mixture is extracted with methylene chloride and the extract is dried over sodium sulphate, filtered and concentrated. The remaining oil is purified on a 300 g silica gel column using methylene chloride and then methylene chloride/ethyl acetate (20:1) as the eluting agent. This operation is repeated once on a 120 g silica gel column using methylene chloride and then methylene chloride/ethyl acetate (20:1) as the eluting agent. After crystallisation from ethyl acetate/ether, there is obtained (S)-7-amino-6-chloro-5-(o-fluorophenyl)-1,3-dihydro-1,3-dimethyl-2H-1,4-benzodiazepin-2-one which melts at 222°-226° C.; [α]25D =+92° (in methylene chloride; 0.5%).

Workup

  1. concentrationThe mixture is concentrated at 0°-5° C.
  2. temperaturecooling trap
  3. additionwith a mixture of ice and 10% sodium bicarbonate solution
  4. extractionThe mixture is extracted with methylene chloride
  5. dry with materialthe extract is dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe remaining oil is purified on a 300 g silica gel column
  9. customAfter crystallisation from ethyl acetate/ether

Sources & evidence

ORD record
ord-7ea27a8cb75c405581e17f89bd6af42a
Source dataset
uspto-grants-1981_07
Patent number
US04281188

Reaction notes

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