Sodium hydride → (R)-2-(4-Phenoxy-phenylsulfanylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Temperatur

2.5 °C

To a solution of 4-phenoxy benzenethiol (200 mg, 0.988 mmol) in DMF (3 mL) at 0-5° C. was added 60% NaH (73 mg, 1.83 mmol) at 0-5° C. The reaction mixture was stirred at rt for 15 min at 0-5° C. A solution of (R)-2-(Toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (357 mg, 1 mmol) in DMF (2 mL) was added to the above mixture at 0-5° C. The reaction mixture was warmed to rt and then heated at 90° C. for 15 h. The mixture was concentrated, diluted with saturated aq NaHCO3 and extracted with ethyl acetate. The aqueous layer was re-extracted with ethylacetate. The combined organic layers were dried over anhy. MgSO4 and the solvent was removed in vacuo to obtain the crude mixture, which was purified by silica gel flash chromatography to obtain the title product (272 mg, 71%).

1. temperatureThe reaction mixture was warmed to rt
2. temperatureheated at 90° C. for 15 h
3. concentrationThe mixture was concentrated
4. additiondiluted with saturated aq NaHCO3
5. extractionextracted with ethyl acetate
6. extractionThe aqueous layer was re-extracted with ethylacetate
7. customThe combined organic layers were dried over anhy
8. customMgSO4 and the solvent was removed in vacuo
9. customto obtain the crude mixture, which
10. customwas purified by silica gel flash chromatography

ORD-Eintrag

ord-b0908b828701447095a16a7efea846ac

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08598359B2