Trichloroacetyl chloride → 2,2,2-Trichloro-1-{10-[(2'-methyl-1,1'-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone

HRID 2244227Notes

Reaction equation

HRID 2244227 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([N:16]2[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[CH2:20][N:19]3[CH:27]=[CH:28][CH:29]=[C:18]3[CH2:17]2)=[O:15])[CH:9]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:36][C:37]([Cl:42])([Cl:41])[C:38](Cl)=[O:39]>O1CCCC1.C(OCC)(=O)C>[Cl:36][C:37]([Cl:42])([Cl:41])[C:38]([C:27]1[N:19]2[C:18]([CH2:17][N:16]([C:14]([C:10]3[CH:9]=[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[CH3:1])[CH:13]=[CH:12][CH:11]=3)=[O:15])[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[CH2:20]2)=[CH:29][CH:28]=1)=[O:39]

Participants

6

Reactant 3

HCID 6420Trichloroacetyl chlorideHCID 10340Sodium CarbonateHCID 6868820210-[(2'-Methyl-1,1'-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

Product 1

HCID 686873312,2,2-Trichloro-1-{10-[(2'-methyl-1,1'-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanoneYield 50.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 10-[(2′-methyl-1,1′-biphenyl-3-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine of Step B (1.7 g, 4.5 mmol) and sodium carbonate (0.95 g, 9.0 mmol) in dry tetrahydrofuran (40 mL) was added dropwise trichloroacetyl chloride (0.75 mL, 6.7 mmol) and the reaction mixture stirred at room temperature under nitrogen for 18 hours. The reaction mixture was then diluted with ethyl acetate (150 mL), washed with 1 M hydrochloric acid (150 mL), water (150 mL) and brine (150 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a dark foam. Purification by flash chromatography using a solvent gradient of 60% to 80% dichloromethane in hexane afforded a white solid that was recrystallized from hot ethyl acetate to give the title compound (1.2 g, 50%) as a white needles.

Workup

  1. washwashed with 1 M hydrochloric acid (150 mL), water (150 mL) and brine (150 mL)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give a dark foam
  5. customPurification by flash chromatography
  6. customafforded a white solid
  7. customthat was recrystallized from hot ethyl acetate

Sources & evidence

ORD record
ord-f7fbb80d9afa46d4b40674c92c3e56f8
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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