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

HRID 217496Notes

Reaction equation

HRID 217496 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[CH:16]([C:19]1[CH:20]=[CH:21][C:22]([O:37][CH3:38])=[C:23]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:26]=2[CH2:35][NH2:36])[CH:24]=1)([CH3:18])[CH3:17].[BH3-]C#N.[Na+].O>CO.C(O)(=O)C>[CH:16]([C:19]1[CH:20]=[CH:21][C:22]([O:37][CH3:38])=[C:23]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:32])([F:33])[F:34])=[CH:27][C:26]=2[CH2:35][NH:36][CH2:7][C:6]2[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH:24]=1)([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 534040393-Nitro-5-(trifluoromethyl)benzaldehydeHCID 591351271-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

Product 1

HCID 59343863{[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-nitro-5-(trifluoromethyl)benzyl]amine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of 3-nitro-5-(trifluoromethyl)benzaldehyde (366 mg, 1.67 mmol) in MeOH (4 mL) was added a solution of 1-[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine (270 mg, 0.84 mmol) in MeOH (4 mL) followed by addition of NaCNBH3 (105 mg, 1.67 mmol) and one drop of acetic acid. The reaction was stirred for 24 hours at room temperature and then poured into H2O (30 mL). The mixture was extracted with EtOAc (60 mL), and the organic extracts were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 2% to 25% EtOAc/hexanes afforded {[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-nitro-5-(trifluoromethyl)benzyl]amine as a yellow oil. Rf=0.45 (15% EtOAc/hexanes). LCMS=527.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 8.33 (s, 1H), 8.27 (s, 1H), 7.85 (s, 1H), 7.74 (s, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.22 (dd, J=8.5 Hz, 2.0 Hz, 1H), 6.97 (d, J=2.0 Hz, 1H), 6.89 (d, J=8.5 Hz, 1H), 3.67-3.78 (m, 4H), 3.70 (s, 3H), 2.87 (m, 1H), 1.25 (d, J=7.0 Hz, 6H).

Workup

  1. extractionThe mixture was extracted with EtOAc (60 mL)
  2. washthe organic extracts were washed with brine (20 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-b77d280c0b12443683adefb7346a2015
Source dataset
uspto-grants-2012_06
Patent number
US08193365B2

Reaction notes

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