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

HRID 217495Notes

Reaction equation

HRID 217495 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[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][NH2:21])[CH:9]=1)([CH3:3])[CH3:2].[F:24][C:25]([F:39])([F:38])[C:26]1[CH:27]=[C:28]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:29]Br.C[Si]([N-][Si](C)(C)C)(C)C.[K+].O>C1COCC1.C1(C)C=CC=CC=1>[F:24][C:25]([F:38])([F:39])[C:26]1[CH:27]=[C:28]([CH:31]=[C:32]([C:34]([F:37])([F:35])[F:36])[CH:33]=1)[CH2:29][NH:21][CH2:20][C:11]1[CH:12]=[C:13]([C:16]([F:17])([F:18])[F:19])[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:22][CH3:23]

Participants

7

Reactant 4

HCID 962WaterHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 591351271-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

Product 1

HCID 59343883[3,5-Bis(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-[5′-Isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine (94.1 mg, 0.291 mmol) was dissolved in THF (4 mL). 3,5-B is(trifluoromethyl)benzyl bromide (320 μL, 1.75 mmol) was added followed by potassium bis(trimethylsilyl)amide (2.33 mL of a 0.5 M solution in toluene, 1.164 mmol). The reaction was stirred at room temperature for 72 hours and then poured into H2O (30 mL). The mixture was extracted with EtOAc (75 mL). The organic layer was washed with brine (25 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 0 to 15% EtOAc/hexanes, then a second column with 50% CH2Cl2, then a third column with 25% EtOAc/hexanes afforded [3,5-bis(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine as a light yellow oil. Rf=0.18 (40% CH2Cl2/hexanes). LCMS=550.3 (M+1)+. 1H NMR (CDCl3, 600 MHz) δ 7.75 (s, 1H), 7.74 (s, 1H), 7.70 (s, 2H), 7.58 (d, J=7.9 Hz, 1H), 7.34 (d, J=7.8 Hz, 1H), 7.24 (dd, J=8.5, 2.2 Hz, 1H), 6.99 (d, J=2.2 Hz, 1H), 6.90 (d, J=8.5 Hz, 1H), 3.68-3.76 (m, 4H), 3.68 (s, 3H), 2.88 (m, 1H), 1.22 (d, J=6.4 Hz, 6H).

Workup

  1. extractionThe mixture was extracted with EtOAc (75 mL)
  2. washThe organic layer was washed with brine (25 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography with 0 to 15% EtOAc/hexanes

Sources & evidence

ORD record
ord-292bfab5082b4770b7a694116c1250d2
Source dataset
uspto-grants-2012_06
Patent number
US08193365B2

Reaction notes

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