Water → Methyl {[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-(trifluoromethyl)benzyl]carbamate

HRID 217494Notes

Reaction equation

HRID 217494 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:26][CH3:27])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=2[CH2:20][NH:21][C:22](=[O:25])[O:23][CH3:24])[CH:9]=1)([CH3:3])[CH3:2].[F:28][C:29]([F:39])([F:38])[C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33]Br.C[Si]([N-][Si](C)(C)C)(C)C.[K+].O>C1COCC1.C1(C)C=CC=CC=1>[CH3:24][O:23][C:22](=[O:25])[N:21]([CH2:20][C:11]1[CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:10]=1[C:8]1[CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=[CH:6][C:7]=1[O:26][CH3:27])[CH2:33][C:32]1[CH:35]=[CH:36][CH:37]=[C:30]([C:29]([F:28])([F:38])[F:39])[CH:31]=1

Participants

7

Reactant 4

HCID 962WaterHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 59343870Methyl {[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Product 1

HCID 11635228Methyl {[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-(trifluoromethyl)benzyl]carbamate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl {[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (20 mg, 0.053 mmol) was dissolved in THF (1 mL). 3-(Trifluoromethyl) benzyl bromide (122 μL, 0.79 mmol) was added followed by potassium bis(trimethylsilyl)amide (320 μL of a 0.5 M solution in toluene, 0.160 mmol). The reaction was stirred for two hours and then 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 2% to 25% EtOAc/hexanes afforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-(trifluoromethyl)benzyl]carbamate. Rf=0.67 (15% EtOAc/hexanes). LCMS=540.3 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 7.72 (s, 1H), 7.36 (dd, J=8.0, 1.0 Hz, 1H), 7.19-7.23 (m, 2H), 7.03-7.07 (m, 3H), 6.86 (m, 2H), 6.57 (d, J=8.5 Hz, 1H), 4.41 (s, 2H), 4.05 (s, 2H) 3.36 (s, 3H), 3.22 (s, 3H), 3.73 (m, 1H), 1.25 (d, J=6.5 Hz, 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 2% to 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-73e2c20ee7ae4d6792c9c18a48c47d86
Source dataset
uspto-grants-2012_06
Patent number
US08193365B2

Reaction notes

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