(Diethylamino)sulfur trifluoride → 4-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(fluoromethyl)cyclohexyl)benzenesulfonamide

HRID 1011530Notes

Reaction equation

HRID 1011530 reaction equation
CCN(S(F)(F)[F:7])CC.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([N:20]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]3[O:37][CH:38]=[CH:39][N:40]=3)=[CH:32][C:31]=2[F:41])[C@@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]2[CH2:27]O)(=[O:19])=[O:18])=[CH:13][CH:12]=1>C(Cl)Cl>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([S:17]([N:20]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]3[O:37][CH:38]=[CH:39][N:40]=3)=[CH:32][C:31]=2[F:41])[C@@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]2[CH2:27][F:7])(=[O:19])=[O:18])=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 59497783HCID 59497783, compound

Product 1

HCID 594977904-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(fluoromethyl)cyclohexyl)benzenesulfonamideYield 33.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DAST (4-dimethylamino-N-methyl-4-stilbazolium tosylate, 9 μL, 0.06 mmol) was added to a solution of 4-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (25 mg, 0.05 mmol) in 2 mL anhydrous methylene chloride at −20° C. The reaction was stirred at room temperature for 1 h, then purified by flash chromatography on silica gel with 0 to 50% ethyl acetate in hexane to yield 4-chloro-N-(2-fluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(fluoromethyl)cyclohexyl)benzenesulfonamide (8 mg, 33%). 1H NMR (400 MHz, CDCl3) δ ppm 7.82 (1H, dd, J=8.06, 1.51 Hz), 7.69-7.78 (4H, m), 7.67 (1H, dd, J=10.83, 1.51 Hz), 7.40-7.49 (2H, m), 7.23-7.26 (1H, m), 4.46 (2H, dd, J=34.50, 15.61 Hz), 3.97-4.22 (2H, m), 3.58 (1H, br. s.), 1.75-1.76 (1H, m), 1.59-1.74 (3H, m), 1.46 (2H, br. s.), 0.94-1.30 (3H, m). 19F NMR (376 MHz, CDCl3) δ ppm −111.85 (s), −118.19 (s). Analytical HPLC R.T.=25.91 min. MS [M+H]30 =481, [M+Na+]=503. HRMS [M+H]+ calc'd 481.1164, found 481.1176. Chiral LC: R.T.=6.08 min., >96% ee.

Workup

  1. custompurified by flash chromatography on silica gel with 0 to 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-af91b83386d047e895366694b152562f
Source dataset
uspto-grants-2011_07
Patent number
US07977362B2

Reaction notes

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