Reaction #61088

Reaction equation

N-methylmorpholine

tert-butoxycarbonylamino-(4-trifluoromethane-sulfonyloxy-phenyl)-acetic acid benzyl ester

diethylphosphite

→

tert-butoxycarbonylamino-[4-(diethoxy-phosphoryl)-phenyl]-acetic acid benzyl ester

Yield 93.1%

Solvents

ethyl acetate

ethyl acetate

acetonitrile

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   Temperaturethen cooled to room temperature
3. 3
   workup.ADDITIONThe mixture was poured into a separatory funnel
4. 4
   Washwashed with 0.2M aqueous hydrochloric acid (2×), water (2×), brine
5. 5
   Dryingdried over sodium sulfate
6. 6
   OtherThe solvent was removed in vacuo
7. 7
   Otherthe product was chromatographed over silica gel gradient
8. 8
   Washeluted between 10 to 75% ethyl acetate in hexanes

Procedure

To a solution of tert-butoxycarbonylamino-(4-trifluoromethane-sulfonyloxy-phenyl)-acetic acid benzyl ester (2.2 g, 4.50 mmol) in acetonitrile (10 mL) was added diethylphosphite (643 μL, 5.00 mmol) followed by N-methylmorpholine (691 μL, 6.30 mmol). The mixture was purged with nitrogen and tetrakis-triphenylphosphine palladium (260 mg, 0.23 mmol, 15 mol %) was added. The reaction mixture was heated to 75° C. overnight then cooled to room temperature and diluted with ethyl acetate (50 mL). The mixture was poured into a separatory funnel containing ethyl acetate (100 mL) and washed with 0.2M aqueous hydrochloric acid (2×), water (2×), brine and dried over sodium sulfate. The solvent was removed in vacuo, and the product was chromatographed over silica gel gradient eluted between 10 to 75% ethyl acetate in hexanes to afforded tert-butoxycarbonylamino-[4-(diethoxy-phosphoryl)-phenyl]-acetic acid benzyl ester (2.0 g, 93%).

Source