反应详情

温度

65 °C

A flask was purged with nitrogen and charged with 2-methyl-4-nitro-benzoic acid (45.3 g, 0.25 mol), trimethyl borate (103.9 g, 1.00 mol), and tetrahydrofuran (906 mL). Neat borane dimethyl sulfide complex (39.9 g, 49.8 mL, 0.525 mol) was added drop-wise at 20-35° C. over at least 30 min. An exotherm and effervescence were observed during this addition. When the addition was complete, the reaction mixture was stirred at 65° C. for at least 2 h or until in-process HPLC analysis showed that conversion was greater than 97%. The batch was quenched with cooling by drop-wise addition of methanol (46 mL), followed by a solution of 12.1 N aqueous hydrochloric acid (97 g, 82.1 mL, 1.00 mol) in water (138 mL) over at least 30 min. Batch temperature was held at 20-35° C. during quench; an exotherm and effervescence were observed during the quench. The mixture was stirred at 50° C. for at least 1 h and concentrated under reduced pressure to a volume of ˜230 mL (to remove tetrahydrofuran). The concentrate was diluted with water (453 mL) and extracted with ethyl acetate (2×453 mL). The organic layer was washed with saturated aqueous sodium chloride solution (230 mL), dried over anhydrous magnesium sulfate (23 g), filtered, and concentrated in vacuo to dryness to give the title compound as a beige solid (41 g, 98% yield).

1. customA flask was purged with nitrogen
2. additionNeat borane dimethyl sulfide complex (39.9 g, 49.8 mL, 0.525 mol) was added drop-wise at 20-35° C. over at least 30 min
3. additionAn exotherm and effervescence were observed during this addition
4. additionWhen the addition
5. customThe batch was quenched
6. temperaturewith cooling by drop-wise addition of methanol (46 mL)
7. customwas held at 20-35° C.
8. customduring quench
9. stirringThe mixture was stirred at 50° C. for at least 1 h
10. concentrationconcentrated under reduced pressure to a volume of ˜230 mL (to remove tetrahydrofuran)
11. additionThe concentrate was diluted with water (453 mL)
12. extractionextracted with ethyl acetate (2×453 mL)
13. washThe organic layer was washed with saturated aqueous sodium chloride solution (230 mL)
14. dry with materialdried over anhydrous magnesium sulfate (23 g)
15. filtrationfiltered
16. concentrationconcentrated in vacuo to dryness