3-Nitrosalicylic acid → (2-hydroxy-3-nitrophenyl)-((R)-3-hydroxypyrrolidin-1-yl)methanone

A mixture of 4.86 g (26 mmol, 1 eq) of 3-nitrosalicylic acid and 12.16 g (26 mmol, 1 eq) of bromotripyrrolidinophosphonium hexafluorophosphate in 65 ml of dichloromethane and in the presence of 13.7 ml (78 mmol, 3 eq) of N,N-diisopropylethylamine was stirred at ambient temperature for 30 minutes. 4.52 g (4.10 mmol, 2 eq) of (R)-(+)-3-pyrrolidinol in solution in 10 ml of dichloromethane were added dropwise and the reaction medium was stirred at ambient temperature overnight. The reaction medium was extracted with a 1 N sodium hydroxide solution and separated by settling out. The aqueous phase was acidified with a 1N hydrochloric acid solution and extracted with ethyl acetate (5×150 ml). The organic phases were combined, dried over magnesium sulfate, filtered and evaporated. 7.83 g of (2-hydroxy-3-nitrophenyl)-((R)-3-hydroxypyrrolidin-1-yl)methanone were obtained in the form of a golden yellow amorphous solid. Crude yield>100%. HPLC: 93% [252].

1. extractionThe reaction medium was extracted with a 1 N sodium hydroxide solution
2. customseparated
3. extractionextracted with ethyl acetate (5×150 ml)
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. customevaporated

ORD record

ord-94b00f06aa394a758500ff4611f3d66e

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090596B2