Water → 4-(4-Chloro-benzenesulfonyl)-3-methyl-4-(2,3,6-trifluoro-phenyl)-butyric acid methyl ester

HRID 1047487Notes

Reaction equation

HRID 1047487 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[C:17]([F:18])=[C:16]([F:19])[CH:15]=[CH:14][C:13]=2[F:20])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:21]([O:26][CH3:27])(=[O:25])/[CH:22]=[CH:23]/[CH3:24].CC(C)([O-])C.[K+].O>C1COCC1.C(OCC)(=O)C>[CH3:27][O:26][C:21](=[O:25])[CH2:22][CH:23]([CH3:24])[CH:11]([S:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)(=[O:10])=[O:9])[C:12]1[C:13]([F:20])=[CH:14][CH:15]=[C:16]([F:19])[C:17]=1[F:18]

Participants

7

Reactant 4

HCID 962WaterHCID 638132Methyl CrotonateHCID 23665647Potassium tert-butoxideHCID 589503342-(4-Chloro-benzenesulfonylmethyl)-1,3,4-trifluoro-benzene

Product 1

HCID 589501144-(4-Chloro-benzenesulfonyl)-3-methyl-4-(2,3,6-trifluoro-phenyl)-butyric acid methyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(4-Chloro-phenylsulfanylmethyl)-1,3,4-trifluoro-benzene (Example 8, step 2, 1.0 g, 3.1 mmol) and methyl crotonate (1.55 g, 15.5 mmol) were dissolved in 50 mL of THF and potassium t-butoxide (1M in THF, 6.2 mL) was added. The reaction mixture was stirred at room temperature for five hours. 100 mL of water and 100 mL of EtOAc were added. The organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated. The product was purified by column chromatography using EtOAc/hexane as the eluent (gradient from 0/100 to 50/50 in 40 min, 0.79 g, 60%). The product is a mixture of diastereomers. 1H NMR (CDCl3 400 MHz) δ 7.60 (m, 2H), 7.37 (m, 2H), 7.07 (m, 1H), 6.83 (m, 0.5H), 6.63 (m, 0.5H), 5.03 (t, J=10.2 Hz, 0.5H), 4.80 (d, J=10.2 Hz, 0.5H), 3.71 (s, 1.5H), 3.60 (s, 1.5H), 3.33 (m, 1H), 3.10 (m, 0.5H), 2.89 (m, 0.5H), 2.42 (m, 0.5H), 2.15 (m, 0.5H), 1.49 (t, J=6.6 Hz, 1.5H), 0.95 (dd, J=8.8 and 7.3 Hz, 1.5H).

Workup

  1. washThe organic layer was washed with brine (100 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe product was purified by column chromatography
  5. customas the eluent (gradient from 0/100 to 50/50 in 40 min, 0.79 g, 60%)
  6. additiona mixture of diastereomers

Sources & evidence

ORD record
ord-fdbce0ec37274ec6aaf75f6a263f692a
Source dataset
uspto-grants-2013_10
Patent number
US08569521B2

Reaction notes

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