tert-butyl N-(4-chlorophenyl)carbamate

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

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

Conditions: temp:50.01; pressure:0.00; stir:

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A Schlenk tube was charged with CuI (9.6 mg, 0.050 mmol, 5.0 mol %), 4-bromo-1-chlorobenzene (192 mg, 1.00 mmol), tert-butyl carbamate (142 mg, 1.21 mmol), K2CO3 (280 mg, 2.03 mmol), briefly evacuated and backfilled with argon. N,N′-Dimethylethylenediamine (11 μL, 0.10 mmol, 10 mol %) and toluene (1.0 mL) were added under argon. The Schlenk tube was sealed with a Teflon valve and the reaction mixture was stirred at 110° C. for 23 h. The resulting pale blue suspension was allowed to reach room temperature and filtered through a 0.5×1 cm pad of silica gel eluting with ethyl acetate (10 mL). The filtrate was concentrated and the residue was purified by flash chromatography on silica gel (2×20 cm; hexane-ethyl acetate 9:1; 15 mL fractions). Fractions 12-22 provided 178 mg (78% yield) of the product as white crystals. briefly evacuated The Schlenk tube was sealed with a Teflon valve to reach room temperature filtered through a 0.5×1 cm pad of silica gel eluting with ethyl acetate (10 mL) The filtrate was concentrated the residue was purified by flash chromatography on silica gel (2×20 cm; hexane-ethyl acetate 9:1; 15 mL fractions)

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 11.4 g of tert-butyl 4-chlorophenylcarbamate in 100 ml of ether is cooled to −40° C. under an atmosphere of dry nitrogen, 80 ml of a 1.5 M solution of tert-butyllithium in pentane are added dropwise and the mixture is left stirring at −20° C. for 3 hours. The reaction mixture is cooled to −40° C., a solution-of 14 g of the compound obtained in step A in 50 ml of THF is added over 1 hour and the mixture is left stirring for 4 days at RT. The reaction mixture is poured into saturated NH4Cl solution and the precipitate formed is spin-filtered off and dried. 10.2 g of the expected product are obtained and are used without further purification in the following step. the mixture is left The reaction mixture is cooled to −40° C. the mixture is left stirring for 4 days at RT the precipitate formed is spin-filtered off dried

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a room temperature solution of 4-chloro-phenylamine (5.0 g, 39.19 mmol) was added di-tert-butyl dicarbonate (9.41 g, 43.11 mmol) portion-wise. The solution was heated to reflux, stirred for 2 hrs, cooled, concentrated, and dissolved in diethylether. The solution was washed with water, sodium bicarbonate and brine, dried over MgSO4, filtered, and concentrated to provide (4-chloro-phenyl)-carbamic acid tert-butyl ester (8.5 g) as a white solid, which was used with no further purification. To a −78° C. solution of (4-chloro-phenyl)-carbamic acid t-butyl ester (5.046, 23.30 mmol) in THF (232 mL) was added 32.9 mL of t-BuLi (1.7 M in pentane, 55.92 mmol) via cannula. The solution was stirred 10 min, warmed to −20° C. and stirred 2 hours further. To the −20° C. red solution was added t-butyl isocyanate (3.33 mL, 29.13 mmol). The solution was stirred at −20° C. for 1 hr, warmed to room temperature, stirred 2 hrs, then heated to reflux and stirred for 12 hrs. The reaction was cooled to room temperature, concentrated and dissolved in diethylether. The solution was washed with water, sodium bicarbonate and brine, dried over MgSO4, filtered, and concentrated to provide 5.87 g of white solid (100%). 1H NMR (300 MHz, CDCl3) δ ppm 1.76 (s, 9H), 6.91 (d, J=8.6 Hz, 1H), 7.48 (dd, J=2.2, 8.5 Hz, 1H), 7.97 (d, J=2.3 Hz, 1H), 9.22 (br s, 1H). was used with no further purification stirred 2 hours further The solution was stirred at −20° C. for 1 hr warmed to room temperature stirred 2 hrs heated to reflux stirred for 12 hrs The reaction was cooled to room temperature concentrated dissolved in diethylether The solution was washed with water, sodium bicarbonate and brine dried over MgSO4 filtered concentrated

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a room temperature solution of 4-chloro-phenylamine (5.0 g, 39.19 mmol) was added di-tert-butyl dicarbonate (9.41 g, 43.11 mmol) portion-wise. The solution was heated to reflux, stirred for 2 hrs, cooled, concentrated, and dissolved in diethylether. The solution was washed with water, sodium bicarbonate and brine, dried over MgSO4, filtered, and concentrated to provide (4-chloro-phenyl)-carbamic acid tert-butyl ester (8.5 g) as a white solid, which was used with no further purification. To a −78° C. solution of (4-chloro-phenyl)-carbamic acid t-butyl ester (5.046, 23.30 mmol) in THF (232 mL) was added 32.9 mL of t-BuLi (1.7 M in pentane, 55.92 mmol) via cannula. The solution was stirred 10 min, warmed to −20° C. and stirred 2 hours further. To the −20° C. red solution was added t-butyl isocyanate (3.33 mL, 29.13 mmol). The solution was stirred at −20° C. for 1 hr, warmed to room temperature, stirred 2 hrs, then heated to reflux and stirred for 12 hrs. The reaction was cooled to room temperature, concentrated and dissolved in diethylether. The solution was washed with water, sodium bicarbonate and brine, dried over MgSO4, filtered, and concentrated to provide 5.87 g of white solid (100%). 1H NMR (300 MHz, CDCl3) δ ppm 1.76 (s, 9H), 6.91 (d, J=8.6 Hz, 1H), 7.48 (dd, J=2.2, 8.5 Hz, 1H), 7.97 (d, J=2.3 Hz, 1H), 9.22 (br s, 1H). was used with no further purification stirred 2 hours further The solution was stirred at −20° C. for 1 hr warmed to room temperature stirred 2 hrs heated to reflux stirred for 12 hrs The reaction was cooled to room temperature concentrated dissolved in diethylether The solution was washed with water, sodium bicarbonate and brine dried over MgSO4 filtered concentrated

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

Procedure: In a manner similar to that described above for compound 1aa, 4-Chloro-N-Boc-aniline and 2-chloro-6-fluoro-benzoyl chloride were converted to 1ab (42% yield) MS m/z=284 (M+H).

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

Procedure: In a manner similar to that described above for compound 1aa, 4-Chloro-N-Boc-aniline and 2,4-difluoro-benzoyl chloride were converted to 1w (20% yield) MS m/z=268 (M+H).

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

Procedure: In a manner similar to that described above for compound 1aa, 4-Chloro-N-Boc-aniline and 2,4-difluoro-benzoyl chloride were converted to 1w (20% yield) MS m/z=268 (M+H).

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

Procedure: In a manner similar to that described above for compound 1aa, 4-Chloro-N-Boc-aniline and 2,3-difluoro-benzoyl chloride were converted to 1v (14% yield) MS m/z=268 (M+H).