Methanesulfonyl chloride → 2-[1-[(4-Chlorophenyl)sulfonyl]cyclopropyl]-1,4-difluorobenzene

HRID 748779Notes

Reaction equation

HRID 748779 reaction equation
C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH:16]([C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=2[F:27])[CH2:17][CH2:18]O)(=[O:15])=[O:14])=[CH:9][CH:8]=1.CS(Cl)(=O)=O>C(OCC)(=O)C.CCCCCC.CCCCCC.O.O1CCCC1>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([C:16]2([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[F:27])[CH2:18][CH2:17]2)(=[O:15])=[O:14])=[CH:9][CH:8]=1

Participants

8

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 230287923-[(4-Chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)-1-propanolHCID 178418339Butyllithium3×

Product 1

HCID 597507752-[1-[(4-Chlorophenyl)sulfonyl]cyclopropyl]-1,4-difluorobenzeneYield 57%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent4×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Under an argon atmosphere and at −78° C., n-butyl lithium (a 1.57M hexane solution, 600 μl, 0.942 mmol) was added to a tetrahydrofuran solution (4 ml) of the 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)-1-propanol (300 mg, 0.865 mmol) obtained in Example 207. After stirring for 5 minutes, methanesulfonyl chloride (70.6 μl, 0.908 mmol) was added. The resulting solution was stirred for further 5 minutes and then, n-butyl lithium (a 1.57M hexane solution, 601 μl, 0.944 mmol) was added thereto. The temperature of the reaction mixture was elevated to room temperature, at which stirring was conducted for 18 hours. After cooling to −78° C., n-butyl lithium (a 1.57M hexane solution, 400 μl, 0.255 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. Water was added, followed by extraction with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate and then, concentrated. The residue thus obtained was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=19:1 eluate was concentrated. The solid thus obtained was recrystallized from ethyl acetate-hexane, whereby the title compound (161 mg, 0.489 mmol, 57%) was obtained as colorless plate crystals.

Workup

  1. stirringThe resulting solution was stirred for further 5 minutes
  2. customwas elevated to room temperature, at which
  3. stirringstirring
  4. waitwas conducted for 18 hours
  5. stirringThe reaction mixture was stirred at room temperature for 3 hours
  6. extractionfollowed by extraction with ethyl acetate
  7. washwashed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue thus obtained
  11. concentrationethyl acetate=19:1 eluate was concentrated
  12. customThe solid thus obtained

Sources & evidence

ORD record
ord-84ccfe63c8bc4de08d44a4767cadc834
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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