Ethyl chloroformate → HCID 14156727, compound

HRID 579977Notes

Reaction equation

HRID 579977 reaction equation
C(=O)(O)[O-].[Na+].[C:6]([N:9]1[CH:15]([CH2:16][CH2:17][CH2:18][N:19](C)[CH3:20])[C:14]2[CH:22]=[CH:23][CH:24]=[C:25]3[CH2:26][CH2:27][N:12]([C:13]=23)[C:11]2[CH:28]=[CH:29][CH:30]=[CH:31][C:10]1=2)(=[O:8])[CH3:7].Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34]>C1C=CC=CC=1.O.ClCCl>[CH2:36]([O:35][C:33](=[O:34])[N:19]([CH2:18][CH2:17][CH2:16][CH:15]1[C:14]2[CH:22]=[CH:23][CH:24]=[C:25]3[CH2:26][CH2:27][N:12]([C:13]=23)[C:11]2[CH:28]=[CH:29][CH:30]=[CH:31][C:10]=2[N:9]1[C:6](=[O:8])[CH3:7])[CH3:20])[CH3:37]

Participants

7

Reactant 3

HCID 10928Ethyl chloroformate4×HCID 516892Sodium BicarbonateHCID 14156725HCID 14156725, compound

Product 1

HCID 14156727HCID 14156727, compound

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred suspension of 27.64 g of powdered anhydrous sodium bicarbonate in 415 ml of benzene containing 23.0 g of 7-acetyl-N,N-dimethyl-1,2,6,7-tetrahydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-6-propanamine was treated with 19.0 ml of ethyl chloroformate. After an overnight reflux under nitrogen, 6.3 ml more of ethyl chloroformate was added, and reflux continued another 2 hours. TLC still showed the presence of the starting material at this point, and a further addition of 6.3 ml of ethyl chloroformate was made. After 2 hours another 12.6 ml of ethyl chloroformate was added, reflux continued for another 1.5 hours, and the mixture cooled to room temperature. The reaction mixture was diluted with 500 ml of distilled water, stirred for a while, and poured into a separatory funnel, and the phases were separated. The aqueous phase was extracted with 250 ml of ethyl acetate. The combined organic phases were extracted with 200 ml of 2N hydrochloric acid, washed with 200 ml of water and 200 ml of saturated sodium chloride solution, and dried over anhydrous sodium sulfate. Filtration and concentration in vacuo afforded a gum weighing 24.37 g. This material was dissolved in 150 ml of dichloromethane, the resulting solution was divided into two halves, and each half was purified by flash chromatography on 500 g of silica gel, using dichloromethane and then 1% methanol/dichloromethane as solvent. The purest fractions were combined and concentrated in vacuo to a foam which partially crystallized upon standing. Trituration with hexane fully solidified this material, which was filtered, washed with hexane and dried in vacuo to afford 11.65 g of solid, m.p. 125°-128° C.

Workup

  1. temperatureAfter an overnight reflux under nitrogen
  2. temperaturereflux
  3. temperaturereflux
  4. waitcontinued for another 1.5 hours
  5. additionpoured into a separatory funnel
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted with 250 ml of ethyl acetate
  8. extractionThe combined organic phases were extracted with 200 ml of 2N hydrochloric acid
  9. washwashed with 200 ml of water and 200 ml of saturated sodium chloride solution
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationFiltration and concentration in vacuo
  12. customafforded a gum
  13. customeach half was purified by flash chromatography on 500 g of silica gel
  14. concentrationconcentrated in vacuo to a foam which
  15. custompartially crystallized
  16. filtrationwas filtered
  17. washwashed with hexane
  18. customdried in vacuo

Sources & evidence

ORD record
ord-602cf1f4a503467a8f5225081d6744f2
Source dataset
uspto-grants-1988_06
Patent number
US04751223

Reaction notes

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