Water → N-[3,5-bis(trifluoromethyl)benzyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}methanesulfonamide

HRID 17066Notes

Reaction equation

HRID 17066 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29].[CH3:39][S:40](Cl)(=[O:42])=[O:41].C(N(CC)C(C)C)(C)C.O>C(Cl)Cl>[F:1][C:2]([F:37])([F:38])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:32]=1)[CH2:6][N:7]([CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[C:23]([CH:25]([CH3:26])[CH3:27])[CH:22]=[CH:21][C:20]=1[O:28][CH3:29])[S:40]([CH3:39])(=[O:42])=[O:41]

Participants

6

Reactant 4

HCID 962WaterHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 59343883[3,5-Bis(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine

Product 1

HCID 11628764N-[3,5-bis(trifluoromethyl)benzyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [3,5-bis(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine (8.3 mg, 0.015 mmol) (Example 20) and methanesulfonyl chloride (10.5 μL, 0.135 mmol) in CH2Cl2 (500 μL) was added N,N-diisopropylethylamine (47.4 μL, 0.273 mmol). The reaction was stirred at room temperature for twenty minutes and then was poured into H2O (10 mL). The mixture was extracted with EtOAc (50 mL), and the organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 50% CH2Cl2/hexanes afforded N-[3,5-bis(trifluoromethyl)benzyl]-N-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}methanesulfonamide. Rf=0.20 (50% CH2Cl2/hexanes). LCMS=628.3 (M+1)+. 1H NMR (CDCl3, 600 MHz) δ 7.69 (s, 1H), 7.55 (s, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.47 (s, 2H), 7.28-7.30 (m, 2H), 6.94 (d, J=9.0 Hz, 1H), 6.92 (d, J=1.8 Hz, 1H), 4.44 (d, J=15.0, 1H), 4.32 (d, J=15.0 Hz, 1H), 4.19 (d, J=15.6 Hz, 1H), 4.14 (d, J=15.6 Hz, 1H), 3.72 (s, 3H), 2.89 (m, 1H), 2.69 (s, 3H), 1.21-1.25 (m, 6H).

Workup

  1. extractionThe mixture was extracted with EtOAc (50 mL)
  2. washthe organic extracts were washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography with 50% CH2Cl2/hexanes

Sources & evidence

ORD record
ord-1ccbb79c5d944ea598b8db17e33699f5
Source dataset
uspto-grants-2010_06
Patent number
US07737295B2

Reaction notes

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