Dimethylformamide → cis-2-(4-Bromobenzoyl)cyclopentanecarboxylic acid methyl ester

HRID 9549Notes

Reaction equation

HRID 9549 reaction equation
O=S(Cl)Cl.CN([CH:8]=[O:9])C.[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Al+3].[Cl-].[Cl-].[Cl-].C[CH2:22][O:23][C:24]([CH3:26])=[O:25]>C(Cl)Cl>[CH3:22][O:23][C:24]([C@@H:26]1[CH2:13][CH2:12][CH2:11][C@@H:16]1[C:8](=[O:9])[C:14]1[CH:15]=[CH:16][C:11]([Br:10])=[CH:12][CH:13]=1)=[O:25]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 7961BromobenzeneHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 67147310cis-2-(4-Bromobenzoyl)cyclopentanecarboxylic acid methyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the monomethyl ester (92.0 g, 534.3 mmol), SOCl2 (116.3 mL, 1.60 mol), and DMF (1 mL) in 850 mL CH2Cl2 was stirred at rt overnight under N2. NMR analysis showed little starting material remaining. The solvent was removed by rotary evaporation at <40° C., and the residue was dried in vacuo for 1 h. This dried residue was dissolved in bromobenzene (337.6 mL, 3.2 mol), and AlCl3 (142.5 g, 1.07 mol) was then added portionwise at <5° C. The reaction mixture turned dark brown, and was stirred at <5° C. for 4 h under N2. NMR analysis then showed little starting material remaining. The reaction mixture was then slowly poured into 2 L ice-water, and then 1 L EtOAc was added. After the mixture was stirred for 10 minutes, the aqueous (top) layer was separated, and extracted with 500 mL EtOAc. The combined organic layers were washed with water (2×1 L) and saturated NaHCO3 solution (200 mL), and dried over Na2SO4. Removal of solvent and drying in vacuo provided 175.0 g (>95%) of the desired product. 1H NMR (CDCl3) δ 7.80 (d, 2H), 7.60 (d, 2H), 4.07 (m, 1H), 3.53 (s, 3H), 3.07 (m, 1H), 2.20 (m, 1H), 2.00 (m, 4H), 1.70 (m, 1H).

Workup

  1. customThe solvent was removed by rotary evaporation at <40° C.
  2. customthe residue was dried in vacuo for 1 h
  3. stirringAfter the mixture was stirred for 10 minutes
  4. customthe aqueous (top) layer was separated
  5. extractionextracted with 500 mL EtOAc
  6. washThe combined organic layers were washed with water (2×1 L) and saturated NaHCO3 solution (200 mL)
  7. dry with materialdried over Na2SO4
  8. customRemoval of solvent
  9. customdrying in vacuo

Sources & evidence

ORD record
ord-814ba5bff74441219c973e99d8628a05
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

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