3-Oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (2.219 kg, 11.44 mol; 99.6 mass %) was charged to a 100 L glass-lined vessel followed by toluene (9 L). Ethyl [(3S)-7-fluoro-3,4-dihydro-2H-1,4-benzoxazin-3-yl]acetate (Intermediate 10a, 2.970 kg, 10.39 mol, 83.7 mass %) was charged and the mixture was stirred at 20° C. A solution of T3P in 2-MeTHF (11.6 L, 20.8 mol, 55.7 mass %) was then charged to the vessel within 5 minutes. Toluene (3.1 L), Pyridine (2.5 L) and toluene (3 L) were charged and the resulting mixture heated at 80° C. for 20 h then cooled to 20° C. and held for 3 days. The mixture was heated to 50° C. and washed with water (15 L). The organic phase was retained and the separated aqueous phase extracted with toluene (14.8 L). The combined organic phase was washed with aqueous sodium bicarbonate solution (14.8 L, 11.3 mol, 6.00 mass %) then water (15 L) at 39-50° C. The organic phase was cooled to 21° C., filtered to remove particulates, and a small amount of collected solid was washed with toluene (3 L). The filtrate was then concentrated to 4 relative volumes by distillation under reduced pressure to yield a solution of ethyl {(3S)-7-fluoro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetate in toluene. The organic phase was filtered once more and a solution of methylamine (33% w/w) in ethanol (13 L, 104 mol, 33.3 mass %) was added and the mixture stirred at 20° C. for 3 days. The mixture was evaporated to dryness under reduced pressure, then treated with 2-propanol (5 L) and re-evaporated. The 2-propanol treatment was repeated once more; 10 Lt was used to rinse the 100 Lt vessel and this was added to the collected product in the rotary evaporator vessel and the mixture evaporated to dryness. The collected solid was further dried in a vacuum oven under reduced pressure (10 mBar). The dried solid (3.985 Kg) was charged to a clean dry vessel, followed by 2-propanol (24.5 L), the mixture was stirred and heated to 80° C., held at 80° C. for 2 h then cooled to 10° C. and held at 10-11° C. for 4 days then filtered. The product cake was washed with 2-propanol (5 L) then dried in a vacuum oven at 45° C. to afford the title product (3.636 Kg; 99.4% w/w assay, 87.1% yield).
