Potassium Carbonate → HCID 14459750, compound

HRID 1904930Notes

Reaction equation

HRID 1904930 reaction equation
C[N:2]1[CH2:7][CH2:6][CH:5]([CH:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[CH2:19][CH2:20][N:12]([C:13]=34)[C:11]3[CH:21]=[CH:22][CH:23]=[CH:24][C:10]=3[N:9]2[C:25]([O:27][CH2:28][C:29]([Cl:32])([Cl:31])[Cl:30])=[O:26])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Cl[C:40]([O:42][CH2:43][C:44]([Cl:47])([Cl:46])[Cl:45])=[O:41].ClC([O-])=O>ClCCl.CCCCCC.O.C1C=CC=CC=1>[Cl:45][C:44]([Cl:47])([Cl:46])[CH2:43][O:42][C:40]([N:2]1[CH2:7][CH2:6][CH:5]([CH:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[CH2:19][CH2:20][N:12]([C:13]=34)[C:11]3[CH:21]=[CH:22][CH:23]=[CH:24][C:10]=3[N:9]2[C:25]([O:27][CH2:28][C:29]([Cl:32])([Cl:31])[Cl:30])=[O:26])[CH2:4][CH2:3]1)=[O:41]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 870632,2,2-Trichloroethyl chloroformateHCID 14459749HCID 14459749, compoundHCID 21226386Carbonochloridate2×

Product 1

HCID 14459750HCID 14459750, compound

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 962WaterSolventHCID 21226440Methylenechloride HexaneSolvent

Procedure

A mixture of 3.43 g of 6-(1-methylpiperidin-4-yl)-1,2,6,7-tetrahydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-7-carboxylic acid, 2,2,2-trichloroethyl ester, 140 ml of benzene and 4.77 g of milled, anhydrous potassium carbonate was stirred under nitrogen and 1.2 ml of 2,2,2-trichloroethyl chloroformate was added. After an overnight reflux, another 1.2 ml of the chloroformate was added and reflux continued for 1 hour. After further addition of another 1.2 ml of chloroformate and another 1.5 hours of reflux, the mixture was allowed to cool to room temperature and 100 ml of distilled water was added. After short period of stirring, the mixture was poured into a separatory funnel and the phases were separated. The aqueous phase was basic to pH paper. It was extracted with 100 ml of ethyl acetate. The combined organic extracts were washed with 50 ml of 2N aqueous hydrochloric acid solution, 100 ml of saturated sodium bicarbonate solution, 100 ml of water and finally 100 ml of saturated sodium chloride solution and thereafter dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate in vacuo afforded a crude product contaminated with excess reagent. Flash chromatography on 280 g of silica gel using 1:1 dichloromethane/hexane as solvent afforded a gum, which was triturated to solid with 2:1 petroleum ether/ether solution. Filtration, washing and drying afforded 3.07 g of solid, m.p. 202°-205° C.

Workup

  1. customof milled
  2. temperatureAfter an overnight reflux
  3. temperaturereflux
  4. temperatureanother 1.5 hours of reflux
  5. additionthe mixture was poured into a separatory funnel
  6. customthe phases were separated
  7. extractionIt was extracted with 100 ml of ethyl acetate
  8. washThe combined organic extracts were washed with 50 ml of 2N aqueous hydrochloric acid solution, 100 ml of saturated sodium bicarbonate solution, 100 ml of water and finally 100 ml of saturated sodium chloride solution
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationFiltration and concentration of the filtrate in vacuo
  11. customafforded a crude product
  12. customwas triturated to solid with 2:1 petroleum ether/ether solution
  13. filtrationFiltration
  14. washwashing
  15. customdrying

Sources & evidence

ORD record
ord-6577780cfb3242469813ee16d6665e2b
Source dataset
uspto-grants-1989_06
Patent number
US04840947

Reaction notes

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