4-Toluenesulfonyl chloride → (4,4-Difluorocyclohexyl)methyl 4-methylbenzenesulfonate

HRID 78543Notes

Reaction equation

HRID 78543 reaction equation
[F:1][C:2]1([F:10])[CH2:7][CH2:6][CH:5]([CH2:8][OH:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[S:18](Cl)([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19]>ClCCl>[CH3:25][C:24]1[CH:26]=[CH:27][C:21]([S:18]([O:9][CH2:8][CH:5]2[CH2:6][CH2:7][C:2]([F:10])([F:1])[CH2:3][CH2:4]2)(=[O:20])=[O:19])=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 21184133(4,4-Difluorocyclohexyl)methanol

Product 1

HCID 23224632(4,4-Difluorocyclohexyl)methyl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 370A (8.5 g, 57 mmol) in dichloromethane (100 mL) were added triethylamine (Aldrich, 25 mL, 180 mmol) and tosyl chloride (Aldrich, 11.4 g, 60 mmol). The reaction mixture was stirred at room temperature for 16 hours and washed with water (50 mL) and brine (50 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% ethyl acetate in hexanes) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.17-1.42 (m, 2H), 1.57-1.69 (m, 1H), 1.70-1.91 (m, 4H), 1.93-2.18 (m, 2H), 2.46 (s, 3H), 3.86 (d, J=6.4 Hz, 2H), 7.35 (d, J=8.5 Hz, 2H), 7.78 (d, J=8.1 Hz, 2H).

Workup

  1. washwashed with water (50 mL) and brine (50 mL)
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-c92cb7336a5a461792ca163a6e4ff1a1
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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