Diethyl Ether → HCID 68688004, compound

HRID 2244266Notes

Reaction equation

HRID 2244266 reaction equation
[I:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][C:3]=1[CH3:24].C(N(CC)C(C)C)(C)C.[Cl:34][C:35]([Cl:40])([Cl:39])[C:36](Cl)=[O:37].C(OCC)C>ClCCl>[Cl:34][C:35]([Cl:40])([Cl:39])[C:36]([C:19]1[N:11]2[C:10]([CH2:9][N:8]([C:6](=[O:7])[C:5]3[CH:22]=[CH:23][C:2]([I:1])=[C:3]([CH3:24])[CH:4]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12]2)=[CH:21][CH:20]=1)=[O:37]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6420Trichloroacetyl chloride2×HCID 81531Diisopropylethylamine2×HCID 68687760HCID 68687760, compound

Product 1

HCID 68688004HCID 68688004, compoundYield 77,627.203%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 10-(4-iodo-3-methylbenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step A (5.0 g, 0.0117 mmol) and N,N-diisopropylethylamine (3.25 mL, 0.0187 mol) in dry dichloromethane (50 mL) at room temperature under nitrogen was added dropwise trichloroacetyl chloride (1.95 mL, 0.0175 mol) and the reaction mixture was stirred at room temperature for 23 hours. Additional N,N-diisopropylethylamine (1.02 mL, 0.00583 mol) and trichloroacetyl chloride (0.65 mL, 0.00583 mol) were added and stirring continued at room temperature for 4 hours. The reaction mixture was then partitioned between dichloromethane (200 mL) and 2 M hydrochloric acid (200 mL). The organic phase was separated, washed with 2 M hydrochloric acid (200 mL) and water (200 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford a black syrup. Purification by flash chromatography using a solvent gradient of 10 to 15% ethyl acetate in hexane gave an orange foam. Diethyl ether (100 mL) was added and the resulting suspension stirred vigorously for 4 hours then filtered to afford the title compound (5.21 g, 78%) as an off-white solid, m.p. 163° C.

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 4 hours
  3. customThe reaction mixture was then partitioned between dichloromethane (200 mL) and 2 M hydrochloric acid (200 mL)
  4. customThe organic phase was separated
  5. washwashed with 2 M hydrochloric acid (200 mL) and water (200 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customto afford a black syrup
  9. customPurification by flash chromatography
  10. customgave an orange foam
  11. stirringthe resulting suspension stirred vigorously for 4 hours
  12. filtrationthen filtered

Sources & evidence

ORD record
ord-f7effff4ebf04fdeab625ced138de4cf
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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