Methanesulfonyl chloride → 4-(Chloromethyl)-5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazole

HRID 1748157Notes

Reaction equation

HRID 1748157 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C@H:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]3[C:15]([F:18])([F:17])[F:16])[C:5]=2[CH2:19]O)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CS([Cl:34])(=O)=O>O>[Cl:34][CH2:19][C:5]1[C:6]([C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[C:15]([F:18])([F:17])[F:16])=[N:7][O:8][C:4]=1[CH:1]1[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 68031448(5-cyclopropyl-3-((1S,2S)-2-(trifluoromethyl)cyclohexyl) isoxazol-4-yl)methanol

Product 1

HCID 867043964-(Chloromethyl)-5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A cold (0°C.) solution of (5-cyclopropyl-3-((1S,2S)-2-(trifluoromethyl)cyclohexyl) isoxazol-4-yl)methanol (1.8 g, 6.2 mmol) dichloromethane was treated with Hunig's base (953 μL, 6.8 mmol) followed by methane sulfonyl chloride (508 L, 6.5 mmol). Afte(6 hr of stirring, the reaction was treated with H2O and phases separated. The organic phase was collected, dried (MgSO4), filtered, concentrated, and chromatographed (SiO2, linear gradient, 0-80% EtOAc in Hex) to give the title compound. 1H NMR (400 MHz, CDCl3) δ 4.48 (dd, J=36.5, 12.6 Hz, 2H), 3.48 (m, 1H), 2.44 (m, 1H), 2.15 (ddd, J=25.5, 12.8, 3.6 Hz, 1H), 2.04-1.87 (m, 4H), 1.82-1.68 (m, 2H), 1.55 (m, 1H), 1.35 (m, 1H), 1.14 (m, 2H), 1.09 (m, 2H), MS m/z 308.1 (M+1).

Workup

  1. customseparated
  2. customThe organic phase was collected
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customchromatographed (SiO2, linear gradient, 0-80% EtOAc in Hex)

Sources & evidence

ORD record
ord-9e7f7bc82f604c8d87034711bb734a93
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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