Hydrogen Bromide → HCID 53662399, compound

HRID 372306Notes

Reaction equation

HRID 372306 reaction equation
[C:1]([CH:6]([C:18](O)=[O:19])[NH:7]C(OCC1C=CC=CC=1)=O)([O:3][CH2:4][CH3:5])=[O:2].P(Cl)(Cl)(Cl)(Cl)Cl.[NH2:27][C:28]1[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:29]=1[C:30]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=O.Br>C(O)(=O)C.C(Cl)Cl.CN(C)C=O>[CH2:4]([O:3][C:1]([CH:6]1[N:7]=[C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:29]2[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:28]=2[NH:27][C:18]1=[O:19])=[O:2])[CH3:5]

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 24819Phosphorus pentachlorideHCID 381721HCID 381721, compoundHCID 111838572-AMINO-4'-CHLOROBENZOPHENONE

Product 1

HCID 53662399HCID 53662399, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 45.0 g. of 2-carbethoxy-N-(benzyloxycarbonyl)glycine in 120 ml. of dry methylene chloride, cooled to -20° C., is treated portionwise with 30 g. of phosphorus pentachloride and stirred for 30 minutes at -20° C. to -10° C. To the now clear solution, there is added at the same temperature a solution of 27.7 g. of 2-amino-4-chlorobenzophenone and 1 ml. of dimethylformamide in 120 ml. of dry methylene chloride. The mixture is concentrated under reduced pressure at 40°-45° C. The residue in partitioned between methylene chloride and 10% aqueous soda solution and the methylene chloride phase is dried over sodium sulfate and evaporated to dryness. There is obtained a reddish-colored resin of crude 2'-benzoyl-2-[(benzyloxycarbonyl)amino]-2-carbethoxy-5'-chloroacetanilide, which is then immediately reacted with 130 ml. of a 33% solution of hydrobromic acid in glacial acetic acid. After stirring at room temperature for 90 minutes, the obtained solution is concentrated at 45° C. and the oily residue partitioned between water and ether. The aqueous solution is made weakly alkaline with solid sodium bicarbonate while cooling with ice. The separated base is extracted with methylene chloride and the extracts are dried over sodium sulfate and evaporated to dryness. The resulting oil is dissolved in a mixture of 180 ml. of toluene and 180 ml. of glacial acetic acid and heated at 80° C. for 90 minutes. The solution is concentrated to an oil and is crystallized from ether so that there is obtained 8-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid ethyl ester, having a melting point of 214°-217° C. (decomposition). Recrystallization from acetonitrile does not increase the melting point.

Workup

  1. additionA suspension of 45.0 g
  2. additionis treated portionwise with 30 g
  3. additionTo the now clear solution, there is added at the same temperature a solution of 27.7 g
  4. concentrationThe mixture is concentrated under reduced pressure at 40°-45° C
  5. customThe residue in partitioned between methylene chloride and 10% aqueous soda solution
  6. dry with materialthe methylene chloride phase is dried over sodium sulfate
  7. customevaporated to dryness
  8. customThere is obtained a reddish-colored resin of crude 2'-benzoyl-2-[(benzyloxycarbonyl)amino]-2-carbethoxy-5'-chloroacetanilide, which
  9. customis then immediately reacted with 130 ml
  10. concentrationthe obtained solution is concentrated at 45° C.
  11. customthe oily residue partitioned between water and ether
  12. temperaturewhile cooling with ice
  13. extractionThe separated base is extracted with methylene chloride
  14. dry with materialthe extracts are dried over sodium sulfate
  15. customevaporated to dryness
  16. dissolutionThe resulting oil is dissolved in a mixture of 180 ml
  17. temperatureof glacial acetic acid and heated at 80° C. for 90 minutes
  18. concentrationThe solution is concentrated to an oil
  19. customis crystallized from ether so that there

Sources & evidence

ORD record
ord-c8d60dbfee604adaaa184fef85fae7a1
Source dataset
uspto-grants-1978_05
Patent number
US04090027

Reaction notes

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