Formic Acid → HCID 20135407, compound

HRID 579979Notes

Reaction equation

HRID 579979 reaction equation
C(O[C:5](=[O:7])C)(=O)C.C(O)=O.[Br:11][C:12]1[CH:13]=[C:14]2[CH2:23][CH2:22][N:21]3[C:15]2=[C:16]([CH:34]=1)[CH:17]([CH2:28][CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])[NH:18][C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=13.[OH-].[Na+]>C(Cl)(Cl)Cl.O.ClCCl>[Br:11][C:12]1[CH:13]=[C:14]2[CH2:23][CH2:22][N:21]3[C:15]2=[C:16]([CH:34]=1)[CH:17]([CH2:28][CH2:29][CH2:30][N:31]([CH3:32])[CH3:33])[N:18]([CH:5]=[O:7])[C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=13

Participants

8

Reactant 4

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 20135401HCID 20135401, compound

Product 1

HCID 20135407HCID 20135407, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

Acetic anhydride (7.8 ml) and formic acid (12.5 ml) were mixed together and stirred at -10° C. for 1 hour. This solution now containing formic-acetic mixed anhydride was added to a solution of 4-bromo-N,N-dimethyl-1,2,6,7-tetrahydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-6-propanamine (21.3 g) in chloroform (250 ml) at room temperature in one portion. The resulting solution was shaken for 30 minutes The reagent and solvent were removed on a rotary evaporator to give a foam-oil mixture. This was dissolved into dichloromethane and water and the mixture was basified with 10% sodium hydroxide. The organic phase was separated, washed with water and brine (2×250 ml) and dried over anhydrous magnesium sulfate. Removal of the solvent gave an oily crude product. Purification was conducted by flash chromatography on silica gel (140 g) eluted with 2 liters of dichloromethane, 2 liters of 1% methanol/dichloromethane and 2 liters of 2% methanol/dichloromethane. Fractions containing the pure product were combined and concentrated to afford 14.7 g of solid. Recrystallization from ethanol (40 ml) at 0° C. gave 10.6 g of crystals, m.p. 126°-127° C.

Workup

  1. stirringThe resulting solution was shaken for 30 minutes The reagent and solvent
  2. customwere removed on a rotary evaporator
  3. customto give a foam-oil mixture
  4. customThe organic phase was separated
  5. washwashed with water and brine (2×250 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customRemoval of the solvent
  8. customgave an oily crude product
  9. customPurification
  10. washeluted with 2 liters of dichloromethane, 2 liters of 1% methanol/dichloromethane and 2 liters of 2% methanol/dichloromethane
  11. additionFractions containing the pure product
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-511f99aa9a164201a71a5991ebb95798
Source dataset
uspto-grants-1988_06
Patent number
US04751223

Reaction notes

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