Norfludiazepam → HCID 86736052, compound

HRID 1111630Notes

Reaction equation

HRID 1111630 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[NH:17][C:16](=O)[CH2:15][N:14]=[C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[C:12]=2[CH:26]=1.P(Cl)(OCC)(OCC)=O.[N+:36]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])#[C-:37]>O1CCCC1>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]3[CH:37]=[N:36][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[C:16]3[CH2:15][N:14]=[C:13]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[C:12]=2[CH:26]=1

Participants

6

Reactant 4

HCID 4540NorfludiazepamHCID 13139Diethyl chlorophosphateHCID 533707Ethyl isocyanoacetateHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 86736052HCID 86736052, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium t-butoxide, 1.29 g (0.0115 mol) was added to a stirred solution of 2.88 g (0.01 mol) of 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepine-2-one in 50 ml of tetrahydrofuran, that had been cooled in an ice bath and covered with a nitrogen atmosphere. After stirring for 5 minutes, 2.59 g (0.015 mol) diethyl chlorophosphate was added. After stirring for 5 minutes, a mixture of 2.26 g (0.02 mol) of ethyl isocyanoacetate in 50 ml of tetrahydrofuran that had been treated with 2.24 g (0.02 mol) of potassium t-butoxide just prior to the addition, was added. After 5 minutes, the ice bath was removed and the stirring was continued for 15 minutes. The mixture was acidified with 2 ml of glacial acetic acid, diluted with 200 ml of saturated sodium bicarbonate solution and extracted twice with 125 ml portions of toluene. The extracts were dried and evaporated and the residue was crystallized from ether to give the product with mp 195°-197°. For analysis, the material was recrystallized from methylene chloride/ether/hexane to give colorless crystals with mp 195°-196°.

Workup

  1. temperaturehad been cooled in an ice bath
  2. stirringAfter stirring for 5 minutes
  3. additionto the addition
  4. additionwas added
  5. waitAfter 5 minutes
  6. customthe ice bath was removed
  7. waitthe stirring was continued for 15 minutes
  8. additiondiluted with 200 ml of saturated sodium bicarbonate solution
  9. extractionextracted twice with 125 ml portions of toluene
  10. customThe extracts were dried
  11. customevaporated
  12. customthe residue was crystallized from ether
  13. customto give the product with mp 195°-197°
  14. customFor analysis, the material was recrystallized from methylene chloride/ether/hexane
  15. customto give colorless crystals with mp 195°-196°

Sources & evidence

ORD record
ord-668ef83329d44d4f9097e21f07d89a88
Source dataset
uspto-grants-1978_10
Patent number
US04118386

Reaction notes

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