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

HRID 17073Notes

Reaction equation

HRID 17073 reaction equation
N(OC(C)(C)C)=O.[CH3:8][O:9][C:10](=[O:46])[N:11]([CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[C:37](N)[CH:36]=1)[CH2:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[C:23]1[CH:28]=[C:27]([CH:29]([CH3:31])[CH3:30])[CH:26]=[CH:25][C:24]=1[O:32][CH3:33].[ClH:47]>C(#N)C.CCOC(C)=O>[CH3:8][O:9][C:10](=[O:46])[N:11]([CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[C:37]([Cl:47])[CH:36]=1)[CH2:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[C:23]1[CH:28]=[C:27]([CH:29]([CH3:31])[CH3:30])[CH:26]=[CH:25][C:24]=1[O:32][CH3:33]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 11699642Methyl[3-amino-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Product 1

HCID 11635554Methyl[3-chloro-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of CuCl2 (11.9 mg, 0.09 mmol) in acetonitrile (1 mL) was added t-butyl nitrite (11 μL, 0.092 mmol). Next, the solution was cooled to 0° C. and methyl[3-amino-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (41 mg, 0.074 mmol) (Example 33) was added as a solution in acetonitrile (1.5 mL). The reaction was slowly warmed to room temperature. After stirring at room temperature for 2 hours, the mixture was diluted with EtOAc (30 mL) and poured into 20% HCl (5 mL). The organic extracts were washed with 20% HCl (2×5 mL), H2O (10 mL), brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 5% to 80% EtOAc/hexanes afforded methyl[3-chloro-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. Rf=0.65 (15% EtOAc/hexanes). LCMS=574.3 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 7.68 (s, 1H), 7.36 (d, J=7.5 Hz, 1H), 7.30 (s, 1H), 7.08-7.05 (m, 4H), 6.83 (d, J=2.5 Hz, 1H), 6.60 (d, J=8.5 Hz, 1H), 4.35 (broad singlet, 3H), 4.01 (broad singlet, 1H), 3.36 (s, 3H), 3.26 (s, 3H), 2.74 (m, 1H), 1.16 (d, J=7.0 Hz, 6H).

Workup

  1. temperatureThe reaction was slowly warmed to room temperature
  2. washThe organic extracts were washed with 20% HCl (2×5 mL), H2O (10 mL), brine (10 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-8b71d16b9bde46768d7189e84f452d39
Source dataset
uspto-grants-2010_06
Patent number
US07737295B2

Reaction notes

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