Lawesson's reagent → (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholine-3-thione

Temperature

70 °C

A pressure tube was charged with a solution of N—[(R)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-2-chloro-acetamide (2.00 g, 6.9 mmol) in tetrahydrofuran (50 ml). The colorless solution was treated with Lawesson's reagent (2.81 g, 6.9 mmol) to give a yellow suspension. The tube was sealed and the mixture stirred at 70° C. overnight. For the workup, the reaction mixture was diluted with ethyl acetate (300 ml) and extracted with a saturated solution of sodium hydrogen carbonate (75 ml). The organic layer was washed with brine (2×80 ml). The combined aqueous layers were extracted with ethyl acetate (300 ml). The combined organic layers were dried over sodium sulphate and concentrated at reduced pressure. The (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholine-3-thione was obtained as a light yellow gum (1.93 g, 92% of theory) sufficiently pure to be engaged in the next step without further purification. MS (ISP): m/z=302.0 [M+H]+, 304.0 [M+2+H]+.

1. customto give a yellow suspension
2. customThe tube was sealed
3. extractionextracted with a saturated solution of sodium hydrogen carbonate (75 ml)
4. washThe organic layer was washed with brine (2×80 ml)
5. extractionThe combined aqueous layers were extracted with ethyl acetate (300 ml)
6. dry with materialThe combined organic layers were dried over sodium sulphate
7. concentrationconcentrated at reduced pressure

ORD record

ord-bc8f1a1d0e2d419cb3d772527954be0a

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399459B2