mPEG9-CH2COOH

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of the product of step (d) (20 g) in dry tetrahydrofuran (500 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 2.43 g) portionwise. The reaction was stirred at 0° C. for 30 minutes then ethyl bromoacetate (8.19 g) was added dropwise and the reaction was allowed to warm to 20° C. and stirred for a further 3 hours. Ethanol (100 mL) was then added and stirring was continued at 20° C. for 30 minutes. Sodium hydroxide solution (2M, 100 mL) was then added and the resulting mixture was stirred at 20° C. for 2 hours. The reaction mixture was then partitioned between dichloromethane (700 mL) and water (700 mL). The aqueous layer was acidified to pH 1 by the addition of hydrochloric acid (2M) and then extracted with dichloromethane (3×500 mL). The combined organic layers were dried and the solvent removed in vacuo. Purification by chromatography on silica gel (Biotage), eluting with 10% methanol/1% ammonia (specific gravity 0.880) in dichloromethane gave the title compound as a pale yellow oil (15 g). LC retention time 2.18 mins. Mass spectrum m/z 485 [M+] to warm to 20° C. stirred for a further 3 hours stirring was continued at 20° C. for 30 minutes the resulting mixture was stirred at 20° C. for 2 hours The reaction mixture was then partitioned between dichloromethane (700 mL) and water (700 mL) The aqueous layer was acidified to pH 1 by the addition of hydrochloric acid (2M) extracted with dichloromethane (3×500 mL) The combined organic layers were dried the solvent removed in vacuo Purification by chromatography on silica gel (Biotage) eluting with 10% methanol/1% ammonia (specific gravity 0.880) in dichloromethane