Propylphosphonic anhydride → Ethyl {7-bromo-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetate

Participants

Reaction Conditions

Reaction Steps

TEA (0.737 mL, 5.32 mmol) and T3P (50 wt. % in EtOAc, 2.372 mL, 3.99 mmol) were added to a solution of ethyl (7-bromo-3,4-dihydro-2H-1,4-benzoxazin-3-yl)acetate (Intermediate 27, 399 mg, 1.33 mmol) and 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (308 mg, 1.60 mmol) in EtOAc (7 mL). The reaction mixture was heated in a microwave reactor at 150° C. for 2 h. Additional T3P (50 wt. % in EtOAc, 1.2 mL, 2.02 mmol) and TEA (0.3 mL, 2.16 mmol) was added and the mixture was heated in a microwave reactor at 150° C. for another 2 h. EtOAc (50 mL) was added and the mixture washed with sat. aq. Na2CO3 (2×30 mL), HCl (30 mL, 0.5M) and brine, dried through a phase separator and evaporated. The compound was purified by preparative HPLC (Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 35-75% ACN in H2O/ACN/FA 95/5/0.2 buffer over 20 min with a flow of 100 mL/min, UV detection at 254/280 nm). The title compound (366 mg, 58%) was obtained after removal of solvents in vacuo.

Provenance & Evidence