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

HRID 217514Notes

Reaction equation

HRID 217514 reaction equation
[CH3:1][O:2][C:3](=[O:39])[N:4]([CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30](I)[CH:29]=1)[CH2:5][C:6]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=1[C:16]1[CH:21]=[C:20]([CH:22]([CH3:24])[CH3:23])[CH:19]=[CH:18][C:17]=1[O:25][CH3:26].[C:40]([Cu])#[N:41].N>CN(C=O)C>[CH3:1][O:2][C:3](=[O:39])[N:4]([CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:40]#[N:41])[CH:29]=1)[CH2:5][C:6]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=1[C:16]1[CH:21]=[C:20]([CH:22]([CH3:24])[CH3:23])[CH:19]=[CH:18][C:17]=1[O:25][CH3:26]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 86615395Methyl[3-iodo-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamateHCID 178418546HCID 178418546, compound

Product 1

HCID 11664112Methyl[3-cyano-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl[3-iodo-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (Example 119, 508 mg, 0.76 mmol) in DMF (40 mL) was added CuCN (1.7 g, 19.0 mmol). The reaction was stirred at 100° C. for 30 hours. The reaction was poured into aq. NH3 (40 mL) and extracted with EtOAc (3×40 mL). All the collected organic extracts were washed with brine (40 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 5% to 80% EtOAc/hexanes afforded methyl[3-cyano-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. Rf=0.55 (20% EtOAc/hexanes). LCMS=565.3 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 7.63 (s, 1H), 7.43-7.38 (m, 3H), 7.17-7.13 (m, 3H), 6.86 (s, 1H), 6.74 (d, J=8.5 Hz, 1H), 4.37 (broad singlet, 2H), 4.08 (broad singlet, 2H), 3.45 (s, 3H), 3.40 (s, 3H), 2.80 (m, 1H), 1.18 (d, J=7.0 Hz, 6H).

Workup

  1. extractionextracted with EtOAc (3×40 mL)
  2. washAll the collected organic extracts were washed with brine (40 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography with 5% to 80% EtOAc/hexanes

Sources & evidence

ORD record
ord-ccaee966982f4c298c778a9362552a2d
Source dataset
uspto-grants-2012_06
Patent number
US08193365B2

Reaction notes

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