p-Toluenesulfonic acid → HCID 22316603, compound

HRID 497260Notes

Reaction equation

HRID 497260 reaction equation
O[C:2]1(C)[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][CH:3]1[CH2:12][C:13](=[O:15])[CH3:14].[Br:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([OH:27])=O)=[CH:20][CH:19]=1.[CH3:28]C1C=CC(S(O)(=O)=O)=CC=1.N12CCCN=C1CCCCC2>CN(C)C1C=CN=CC=1.O>[Br:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:25](=[O:27])[O:15][C:13]([CH3:14])([CH3:28])[C:12]=2[C:3]2[CH:2]=[CH:7][C:6]([S:8]([CH3:11])(=[O:9])=[O:10])=[CH:5][CH:4]=2)=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 74654Benzeneacetic acid, 4-bromo-HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 22316970HCID 22316970, compound

Product 1

HCID 22316603HCID 22316603, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent

Procedure

A mixture of [2-hydroxy-2-methyl-4-(methylsulfonyl)phenyl]propanone (1.5 g, 6.2 mmol, B. Cameron et al., WO 9619469), 4-bromophenylacetic acid (1.8 g, 8.1 mmol), 1-cyclohexyl-3-(2-morphorynoethyl)carbodiimide metho-p-toluenesulfonate (3.4 g, 8.1 mmol) and 4-(dimethylamino)pyridine (30 mg, 0.25 mmol) was stirred for 18 h at room temperature. 1,8-Diazabicyclo[5.4.0]undec-7-ene (1.9 mL, 12.7 mmol) was added and the mixture was refluxed for 3 h. After cooled to room temperature, H2O (50 mL) was added and extracted with CH2Cl2 (50 mL×2), washed with 2N aqueous HCl (50 mL), dried over MgSO4, and concentrated in vacuo. The reaction mixture was purified by flash chromatography eluting with ethyl acetate/hexane (1/1) to give title compound (1.7 g, 65%).

Workup

  1. temperaturethe mixture was refluxed for 3 h
  2. temperatureAfter cooled to room temperature
  3. extractionextracted with CH2Cl2 (50 mL×2)
  4. washwashed with 2N aqueous HCl (50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe reaction mixture was purified by flash chromatography
  8. washeluting with ethyl acetate/hexane (1/1)

Sources & evidence

ORD record
ord-1d69163ddeeb420387d0da7cb8dc10c1
Source dataset
uspto-grants-2005_09
Patent number
US06949536B2

Reaction notes

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