Sodium hydride → 1-(2-(2-Methoxy-4-nitrophenoxy)ethyl)pyrrolidine

Participants

Reaction Steps

Add NaH (3.2 g, 80 mmol) portionwise to a 0° C. solution of 2-pyrrolidin-1-yl-ethanol (9.4 mL, 80 mmol) in DMF (180 mL). Stir the reaction 15-20 min until gas evolution ceases. Add a solution of 1-chloro-2-methoxy-4-nitro-benzene (15.0 g, 80 mmol) in DMF (100 mL) via cannula. Warm the reaction to 130° C. and stir for approximately 18 h. Cool to RT and dilute with EtOAc (300 mL). Wash with water (2×100 mL). Extract the organic layer with 1 N HCl (3×150 mL). Wash this acidic layer with EtOAc (100 mL) then basify by adding 1 N NaOH (500 mL) until pH=8-9. Extract the now basic aqueous layer with CH2Cl2 (3×150 mL). Dry the organic layer over Na2SO4 and concentrate to provide 8.5 g (40%) of the desired product as an orange solid. MS/ES m/z 267.3 [M+H]+.

Provenance & Evidence