Methylamine → 2-[(3S)-7-Fluoro-3,4-dihydro-2H-1,4-benzoxazin-3-yl]-N-methyl-acetamide

Ethyl [(3S)-7-fluoro-3,4-dihydro-2H-1,4-benzoxazin-3-yl]acetate (Intermediate 10a, 50.0 g, 204.2 mmol) was dissolved in MeOH (150 mL) in a 500 mL jacketed vessel at 20° C. Methylamine (127 mL of a 33% w/w solution in EtOH, 96 g, 1.02 mol) was added in one portion and the mixture stirred at 20° C. over night. The solution was sampled and found not to have reached completion by HPLC analysis. The reaction was left stirring for a further 2 h then additional methylamine in EtOH (25.0 mL of a 33% w/w solution in EtOH; 18.9 g; 200.8 mmol) was added and the solution stirred over night at 20° C. The solution was evaporated in vacuo to an orange oil, then MeOH (300 mL) added and the mixture re-evaporated giving a beige solid, that was ground up using a mortar and pestle, then dried in a vacuum oven at 40° C. for 3 h to yield the title compound (46.3 g, 99.2% yield NMR assay 98.1% w/w, 99.7% e.p. by chiral HPLC %).

1. customat 20° C
2. aliquotThe solution was sampled
3. waitThe reaction was left
4. stirringstirring for a further 2 h
5. addition200.8 mmol) was added
6. stirringthe solution stirred over night at 20° C
7. customThe solution was evaporated in vacuo to an orange oil
8. additionMeOH (300 mL) added
9. customthe mixture re-evaporated
10. customgiving a beige solid, that
11. customdried in a vacuum oven at 40° C. for 3 h

ORDレコード

ord-b3f1ddf8d3ec48ad868459f51ae2cdd4

出典データセット

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09394291B2