tert-butyl N-(2-hydroxypropyl)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:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8.24 g (47.0 mmol) (2-Hydroxy-propyl)-carbamic acid tert-butyl ester were dissolved in 100 ml dichloromethane. 7.8 ml (1.2 equiv.) triethylamine were added and the mixture was cooled to 0° C. At that temperature 4.37 ml (1.2 equiv.) methanesulfonyl chloride were added dropwise. The resulting solution was allowed to reach room temperature and stirred for further 4 h. The mixture was diluted with 100 ml dichloromethane and washed sequentially with a 5% KHSO4-solution, water and brine. The organic phase was dried over anhydrous MgSO4 and concentrated under reduced pressure to give methanesulfonic acid 2-tert-butoxycarbonylamino-1-methyl-ethyl ester in crude form as yellow oil. to reach room temperature washed sequentially with a 5% KHSO4-solution, water and brine The organic phase was dried over anhydrous MgSO4 concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 2-hydroxypropylcarbamate (14.3 g, 81.7 mmol) and Et3N (35.6 ml, 245.1 mmol) in CH2Cl2 (250 mL) at 0° C. was slowly added a solution of methanesulfonyl chloride (9.5 mL, 122.6 mmol) in CH2Cl2 (250 mL). The mixture was stirred at 0° C. for 2 h, diluted with CH2Cl2 (300 mL) and washed with water, 1 N HCl, 5% NaHCO3 and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure to afford 1-(tert-butoxycarbonylamino)propan-2-yl methanesulfonate (19.5 g, 94%) as a light yellow oil. Mass calculated for C9H19NO5S=253.32. found: [M+H]+=254.2. washed with water, 1 N HCl, 5% NaHCO3 and brine The organic layer was dried over MgSO4 concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 2-hydroxypropylcarbamate (14.3 g, 81.7 mmol) and Et3N (35.6 ml, 245.1 mmol) in CH2Cl2 (250 mL) at 0° C. was slowly added a solution of methanesulfonyl chloride (9.5 mL, 122.6 mmol) in CH2Cl2 (250 mL). The mixture was stirred at 0° C. for 2 h, diluted with CH2Cl2 (300 mL) and washed with water, 1N HCl, 5% NaHCO3 and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure to afford 1-(tert-butoxycarbonylamino)propan-2-yl methanesulfonate (19.5 g, 94%) as a light yellow oil. Mass calculated for C9H19NO5S=253.32. found: [M+H]+=254.2. washed with water, 1N HCl, 5% NaHCO3 and brine The organic layer was dried over MgSO4 concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of tert-butyl N-(2-hydroxypropyl)carbamate (5.00 g, 28.54 mmol, 1.00 eq) in DMF (100.00 mL), was added NaH (2.51 g, 62.79 mmol, 2.20 eq) in one portion at 0° C. under N2. The mixture was stirred at 0° C. for 1 hr, then 3-chloro-2-(chloromethyl)prop-1-ene (3.57 g, 28.54 mmol, 1.00 eq) was added to the mixture, the mixture was stirred at 0° C. for 4 hr. TLC showed the reaction was completed. The mixture was poured into water (100 mL) and stirred for 5 min. The aqueous phase was extracted with ethyl acetate (100 mL*2). The combined organic phase was washed with saturated brine (100 mL*2), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (Petroleum ether/Ethyl acetate=10/1) to afford tert-butyl 2-methyl-6-methylene-1,4-oxazepane-4-carboxylate (2.20 g, 9.68 mmol, 33.91% yield) as yellow oil. the mixture was stirred at 0° C. for 4 hr stirred for 5 min The aqueous phase was extracted with ethyl acetate (100 mL*2) The combined organic phase was washed with saturated brine (100 mL*2) dried with anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by silica gel chromatography (Petroleum ether/Ethyl acetate=10/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of tert-butyl N-(2-hydroxypropyl)carbamate (5.00 g, 28.54 mmol, 1.00 eq) in DMF (100.00 mL), was added NaH (2.51 g, 62.79 mmol, 2.20 eq) in one portion at 0° C. under N2. The mixture was stirred at 0° C. for 1 hr, then 3-chloro-2-(chloromethyl)prop-1-ene (3.57 g, 28.54 mmol, 1.00 eq) was added to the mixture, the mixture was stirred at 0° C. for 4 hr. TLC showed the reaction was completed. The mixture was poured into water (100 mL) and stirred for 5 min. The aqueous phase was extracted with ethyl acetate (100 mL*2). The combined organic phase was washed with saturated brine (100 mL*2), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (Petroleum ether/Ethyl acetate=10/1) to afford tert-butyl 2-methyl-6-methylene-1,4-oxazepane-4-carboxylate (2.20 g, 9.68 mmol, 33.91% yield) as yellow oil. the mixture was stirred at 0° C. for 4 hr stirred for 5 min The aqueous phase was extracted with ethyl acetate (100 mL*2) The combined organic phase was washed with saturated brine (100 mL*2) dried with anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by silica gel chromatography (Petroleum ether/Ethyl acetate=10/1)

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

Procedure: Prepared analogously to example 9.1 using methyl 4-(2-hydroxypyridin-3-ylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate and tert-butyl N-(2-hydroxypropyl)-carbamate.

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

Procedure: 2-Nitro-5-fluorophenol (3.0 g) and tert-butyl-N-(2-hydroxypropyl)carbamate were dissolved in THF (20 ml) and triphenylphosphine (7.5 g) and di-tert-butyl-azodicarboxylate were added. The exothermic reaction was cooled in an ice bath. Then the reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated in vacuo and the residue was purified by chromatography (silica gel/dichloromethane: petroleum ether 1:2). The fractions were combined and concentrated in vacuo. The residue was dissolved in dichloromethane and washed with 1M NaOH. The organic layer was separated, dried, filtered and concentrated in vacuo. The exothermic reaction was cooled in an ice bath The mixture was concentrated in vacuo the residue was purified by chromatography (silica gel/dichloromethane: petroleum ether 1:2) concentrated in vacuo The residue was dissolved in dichloromethane washed with 1M NaOH The organic layer was separated dried filtered concentrated in vacuo

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

Procedure: 2-Nitro-5-fluorophenol (3.0 g) and tert-butyl-N-(2-hydroxypropyl)carbamate were dissolved in THF (20 ml) and triphenylphosphine (7.5 g) and di-tert-butyl-azodicarboxylate were added. The exothermic reaction was cooled in an ice bath. Then the reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated in vacuo and the residue was purified by chromatography (silica gel/dichloromethane: petroleum ether 1:2). The fractions were combined and concentrated in vacuo. The residue was dissolved in dichloromethane and washed with 1M NaOH. The organic layer was separated, dried, filtered and concentrated in vacuo. The exothermic reaction was cooled in an ice bath The mixture was concentrated in vacuo the residue was purified by chromatography (silica gel/dichloromethane: petroleum ether 1:2) concentrated in vacuo The residue was dissolved in dichloromethane washed with 1M NaOH The organic layer was separated dried filtered concentrated in vacuo