Dimethyl Sulfate → HCID 69672585, compound

A solution of (2S,5R)-1-(tert-butoxycarbonyl)-5-(hydroxymethyl)pyrrolidine-2-carboxylic acid (820 mg, 3.34 mmol) in 11 mL THF was cooled in a −10° C. bath and treated with n-butyl lithium (1.6M in hexanes, 6.5 mL, 10.36 mmol) and kept cold for 1 hour, then dimethyl sulphate (0.380 mL, 4.01 mmol) was added. The temperature was held at −5° C. to 5° C. and then the reaction mixture was held in the −20° C. freezer overnight. The reaction was quenched cold, with water. Next, the mixture was concentrated under reduced pressure to remove THF. The aqueous mixture was acidified with 2N HCl and extracted with ethyl acetate. The organic layer was dried over sodium sulphate, filtered, and concentrated under reduced pressure to give 788 mg crude product, which was then purified by silica gel chromatography to give 199 mg clean product, 140 mg recovered starting material, and 317 mg of a mixture of starting material and product.

1. customwas held at −5° C. to 5° C.
2. customwas held in the −20° C. freezer overnight
3. customThe reaction was quenched cold, with water
4. concentrationNext, the mixture was concentrated under reduced pressure
5. customto remove THF
6. extractionextracted with ethyl acetate
7. dry with materialThe organic layer was dried over sodium sulphate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto give 788 mg crude product, which
11. customwas then purified by silica gel chromatography

ORD record

ord-fc91ad3bb72f4fc580c72f5a63aa4c29

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156823B2