tert-butyl N-[2-(trifluoromethyl)phenyl]carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The titled compound was prepared from tert-butyl 2-(trifluoromethyl)phenylcarbamate using the procedures described in Example 26, Steps 26b through 26h, except for the use of potassium tert-butoxide instead of potassium hexamethyldisilizane in step 26g. MS (ES+) detects free acid at 244 (M+H+).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 2-(trifluoromethyl)phenylcarbamate (1.0 g, 3.83 mmol) and N,N,N′N′-tetramethylethylenediamine (1.27 mL, 8.43 mmol) in 20 mL of anhydrous THF at −78° C. was added sec-butyllithium (8.43 mL of a 1.0 M solution in hexanes, 8.43 mmol) dropwise over 15 min. The reaction was stirred at −78° C. for 1 h and then there was added DMF (0.33 mL, 4.21 mmol). The reaction was stirred at −78° C. for 1 h and then was quenched with sat'd aq NH4Cl (10 mL) and allowed to warm to ambient temperature. The reaction mixture was diluted with water and extracted with EtOAc. The organics were washed with 1N HCl and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (230-400 mesh silica gel, elution with 6:1 hexane/EtOAc) to afford 0.4 g (36%) of the title compound. 1H NMR (CDCl3): δ 10.06 (s, 1H), 8.07 (d, 1H, J=7.7 Hz), 7.83 (d, 1H, J=7.8 Hz), 7.43 (t, 1H, J=7.8 Hz), 6.83 (broad s, 1H), 1.47 (s, 9H). LRMS (ESI): 290.15 (M+H)+. The reaction was stirred at −78° C. for 1 h was quenched with sat'd aq NH4Cl (10 mL) to warm to ambient temperature The reaction mixture was diluted with water extracted with EtOAc The organics were washed with 1N HCl and brine dried (MgSO4) concentrated The residue was purified by flash chromatography (230-400 mesh silica gel, elution with 6:1 hexane/EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-isocyanato-2-(trifluoromethyl)benzene (4.0 g, 21.4 mmol) in 50 mL of THF at 0° C. was added potassium tert-butoxide (32.0 mL of a 1M solution in THF, 32 mmol) dropwise. The reaction was allowed to stir for 3 h with warming to ambient temperature and then was quenched with 10 mL of water. The mixture was diluted with ethyl acetate and the organics were washed sequentially with 1N HCl, sat'd. aq. NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was taken up in chloroform, filtered through a pad of silica gel and concentrated to afford 2.9 g (52%) of the title compound which was sufficiently pure to be used without further purification. 1H NMR (CDCl3): δ 8.13 (d, 1H, J=8.2 Hz), 7.56 (d, 1H, J=7.7 Hz), 7.52 (t, 1H, J=8.0 Hz), 7.14 (t, 1H, J=7.7 Hz), 6.80 (broad s, 1H), 1.53 (s, 9H). was quenched with 10 mL of water The mixture was diluted with ethyl acetate the organics were washed sequentially with 1N HCl aq. NaHCO3 and brine, dried (MgSO4) concentrated filtered through a pad of silica gel concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The titled compound was prepared from tert-butyl 2-(trifluoromethyl)phenylcarbamate using the procedures described in Example 26, Steps 26b through 26h, except for the use of potassium tert-butoxide instead of potassium hexamethyldisilizane in step 26g. MS (ES+) detects free acid at 244 (M+H+).

Conditions: temp:0.00; pressure:0.00; stir: