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

HRID 217510Notes

Reaction equation

HRID 217510 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].[C:39]([O-])(O)=[O:40].[Na+]>C(O)=O>[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])[CH:39]=[O:40]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 59343883[3,5-Bis(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine

Product 1

HCID 11585033[3,5-Bis(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}formamide

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A solution of [3,5-bis(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine (88 mg, 0.43 mmol) (Example 20) in 80% formic acid (3 mL) was heated to and maintained at reflux for 24 hours. The reaction was then cooled to room temperature, poured into saturated NaHCO3 (30 mL), and, after neutralization was complete, extracted with EtOAc (25 mL). The organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 15% EtOAc/hexanes afforded [3,5-bis(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}formamide. Rf=0.20 (15% EtOAc/hexanes). LCMS=578.3 (M+1)+. 1H NMR (CD2Cl2, 600 MHz, rotamers present, ratio of major:minor ˜3:1. Data for major rotamer given.) δ 6.86-8.31 (m, 10H), 4.24-4.47 (m, 4H), 3.71 (s, 3H), 2.87 (m, 1H), 1.27 (m, 6H).

Workup

  1. temperaturemaintained
  2. temperatureat reflux for 24 hours
  3. extractionextracted with EtOAc (25 mL)
  4. washThe organic extracts were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography with 15% EtOAc/hexanes

Sources & evidence

ORD record
ord-ba23bd5c7bd44820a41abde280c7565b
Source dataset
uspto-grants-2012_06
Patent number
US08193365B2

Reaction notes

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