Diisopropylethylamine → (S)-ethyl {7-chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetate

温度

140 °C

T3P (50% solution in EtOAc, 146 g, 230 mmol) was added into a solution of ethyl [(3S)-7-chloro-3,4-dihydro-2H-1,4-benzoxazin-3-yl]acetate (Intermediate 20a, 29.4 g, 115 mmol) in n-BuOAc (100 mL), 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (22.7 g, 118 mmol) and DIPEA (44.5 g, 345 mmol) at 20° C. The resulting mixture was stirred at 140° C. for 24 h. The reaction mixture was cooled and diluted with of EtOAc (500 mL). The resulting mixture was washed with 200 mL of saturated sodium bicarbonate, 200 mL of 1 M citric acid and 200 mL of 1 M HCl. The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to dryness. The residue was applied onto a silica gel column and eluted with EtOAc/PE (1/10 to 1/1). The pure fraction was concentrated in vacuo to afford the title compound (41 g, 83%) as a yellow solid.

1. temperatureThe reaction mixture was cooled
2. washThe resulting mixture was washed with 200 mL of saturated sodium bicarbonate, 200 mL of 1 M citric acid and 200 mL of 1 M HCl
3. dry with materialThe organic phase was dried over anhydrous Na2SO4
4. filtrationfiltered
5. customevaporated to dryness
6. washeluted with EtOAc/PE (1/10 to 1/1)
7. concentrationThe pure fraction was concentrated in vacuo

ORDレコード

ord-87c90b54cc034eca8a690b83560b0de7

出典データセット

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09394291B2