tert-butyl N-(4-hydroxyphenyl)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:

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: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: 2-chloro-thiazole-5-carbonitrile (900 mg 6.2 mmol; prepared according to procedure described in WO 01/17995, p. 103) and N-Boc-4-hydroxy-aniline (1.3 g, 6.2 mmol) were combined in N,N-dimethyl formamide (5 mL). To this solution, K2CO3 (2.6 g, 18.8 mmol) was added and the resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was then poured into water and extracted with ethyl acetate (2×). The combined organics were dried (Na2SO4), filtered and concentrated by rotary evaporation. The residue was purified by flash column chromatography (ethyl acetate:hexanes: 5%-50% ethyl acetate gradient) to give the title compound (2.0 g, 6.2 mmol, 100%) as a white solid. MS (ESI APCI) m/z 316.0 (M−H+); 1H NMR (300 MHz, DMSO-d6) δ 9.59 (s, 1H) 8.24 (s, 1H) 7.58 (d, J=9.0 Hz, 2H) 7.36 (d, J=9.0 Hz, 2H) 1.48 (s, 9H). the resulting reaction mixture extracted with ethyl acetate (2×) The combined organics were dried (Na2SO4) filtered concentrated by rotary evaporation The residue was purified by flash column chromatography (ethyl acetate:hexanes: 5%-50% ethyl acetate gradient)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Boc-4-hydroxy-aniline (3.9 g, 0.019 mol) was combined with 2-bromothiazole (2.4 mL, 0.027 mol) in DMSO (20 mL) at room temperature. K2CO3 (3.9 g, 0.028 mol) was added and with rapid stirring, the reaction mixture was heated at about 140° C. for 5 hours. After cooling to room temperature, the reaction mixture was poured into water (300 mL), extracted with ethyl acetate (2×) and the combined organics were dried over MgSO4. Decolorizing charcoal was added, stirred for 30 minutes and filtered through a plug of celite and silica (1:1) to obtain an amber filtrate. The solvent was removed by rotary evaporation and the residue was purified by flash column chromatography (ethyl acetate:hexanes; 5%-50% ethyl acetate gradient) to give the title compound (1.4 g, 4.8 mmol, 25%) MS (ESI APCI) m/z 293.0 (M+H+); 1H NMR (300 MHz, DMSO-d6) δ 9.49 (s, 1H) 7.53 (d, J=9.0 Hz, 2H) 7.21-7.28 (m, 2H) 7.16-7.19 (m, 2H) 1.48 (s, 9H). After cooling to room temperature extracted with ethyl acetate (2×) the combined organics were dried over MgSO4 Decolorizing charcoal was added filtered through a plug of celite and silica (1:1) to obtain an amber filtrate The solvent was removed by rotary evaporation the residue was purified by flash column chromatography (ethyl acetate:hexanes; 5%-50% ethyl acetate gradient)

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

Procedure: A solution of 9.4 g (52.8 mmoles) of N-bromosuccinimide in 450 mL of chloroform was added dropwise to a suspension 10 g (47.8 mmoles) of tert.butyl N-(4-hydroxy-phenyl)carbamate in 100 mL of chloroform at 0° C. over a period of 2 hours. The reaction mixture was stirred for an additional 15 min and then washed twice with water (first with 400 mL, then with 200 mL), dried over magnesium sulfate, filtered and partly evaporated. Hexane was added to the residue with stirring which caused the formation of a precipitate. The precipitate was filtered off and washed with hexane. washed twice with water (first with 400 mL with 200 mL), dried over magnesium sulfate filtered partly evaporated Hexane was added to the residue with stirring which The precipitate was filtered off washed with hexane