反应详情

Isopropyl acetate (300 mL) was charged into a 1000 ml 3-neck flask and cooled to −10˜−5° C. Sulfurisocyanatidic chloride (44.5 mL) was added at −5˜10° C. followed by the addition of phenylmethanol (50.5 mL) in isopropyl acetate (60 mL) at −5˜10° C. over 60 minutes. The mixture reacted at −5˜10° C. and was monitored by HPLC until the content of benzyl alcohol was <2% (after 1 hour at 0° C.). A mixture of acetonitrile (300 mL), 3-methylazetidine hydrochloride (50 g) (Intermediate C, either commercially available or prepared as set out below) and triethylamine (162 mL) was stirred in a 2000 mL 3-neck flask and to this was added the solution of the intermediate benzyl chlorosulfonylcarbamate in isopropyl acetate (360 mL) dropwise at <−5° C. over 90 minutes. The mixture was allowed to warm to RT overnight. The reaction was quenched with acetic acid and pH was adjusted to 4˜5. The mixture was separated and the aqueous phase was washed with isopropyl acetate (500 ml) and then separated. The organic phase was combined and washed with 10% brine (2×120 ml), dried with anhydrous magnesium sulphate, filtered and the filter cake washed with isopropyl acetate (30 ml) and filtered to afford the sub-title product (145 g) as a red oil.

1. temperaturecooled to −10˜−5° C
2. customThe mixture reacted at −5˜10° C.
3. custom<2% (after 1 hour at 0° C.)
4. customcommercially available or prepared
5. customThe reaction was quenched with acetic acid and pH
6. customThe mixture was separated
7. washthe aqueous phase was washed with isopropyl acetate (500 ml)
8. customseparated
9. washwashed with 10% brine (2×120 ml)
10. dry with materialdried with anhydrous magnesium sulphate
11. filtrationfiltered
12. washthe filter cake washed with isopropyl acetate (30 ml)
13. filtrationfiltered