Oxalyl chloride → HCID 21947764, compound

HRID 2215154Notes

Reaction equation

HRID 2215154 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[CH3:11].C(Cl)(=O)C(Cl)=O.[CH:18]1[CH:19]=[CH:20][N:21]2[CH2:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[NH:24][CH2:23][C:22]=12.CCN(C(C)C)C(C)C>O1CCCC1.ClCCl.CN(C)C=O>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:24]2[C:25]3[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=3[CH2:27][N:21]3[CH:20]=[CH:19][CH:18]=[C:22]3[CH2:23]2)=[O:8])=[CH:4][C:3]=1[CH3:11]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 821314-Bromo-3-methylbenzoic acidHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine

Product 1

HCID 21947764HCID 21947764, compoundYield 1,050.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-bromo-3-methyl benzoic acid (4.3 g, 2 mmol) in dry tetrahydrofuran (100 mL) was cooled to 0° C. under nitrogen. To this was added N,N-dimethylformamide (50 μL) followed by oxalyl chloride (2.2 mL, 25 mmol) dropwise to control the gas evolution. When the gas evolution ceased, the mixture was warmed to reflux for 5 minutes then cooled to room temperature and concentrated in vacuo. The sample was treated with tetrahydrofuran and evaporated to dryness (twice) to yield the crude acid chloride as an orange oil. A solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (3.60 g, 20 mmol) and Hunig's base (4.35 mL, 25 mmol) in dichloromethane was cooled to 0° C., and a solution of the crude acid chloride in dichloromethane (25 mL) was added dropwise. The mixture was stirred overnight at room temperature, washed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate and brine. The solution was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to yield a solid (8.01 g) which was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane to provide the title compound (6.03 g) as a white solid.

Workup

  1. temperaturethe mixture was warmed
  2. temperatureto reflux for 5 minutes
  3. concentrationconcentrated in vacuo
  4. additionThe sample was treated with tetrahydrofuran
  5. customevaporated to dryness (twice)
  6. customto yield the crude acid chloride as an orange oil
  7. washwashed with 1 N hydrochloric acid, saturated aqueous sodium bicarbonate and brine
  8. dry with materialThe solution was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-43e54ec08e8640d398e64fc65c42a05c
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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