Sodium Fluoride → 1,2-Pyrrolidinedicarboxylic acid, 4-fluoro-, 1-(1,1-dimethylethyl) 2-methyl ester, (2R,4R)-rel-

Methyl(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylate (4.91 g, 0.020 mol) and sodium fluoride (1.01 g, 0.024 mol) were suspended in dichloromethane (50 mL), followed by addition of Ishikawa reagent (4.35 mL, 0.024 mol) under ice cooling. The reaction mixture was slowly warmed to room temperature and then stirred for 20 hours. After the reaction, the reaction mixture was poured into ice-cold saturated aqueous sodium bicarbonate (70 mL) and then separated into organic and aqueous layers. The aqueous layer was extracted with ethyl acetate. This extracted solution was combined with the organic layer obtained above, washed sequentially with 10% aqueous potassium bisulfate and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate. After drying, the solvent and the decomposition product of Ishikawa reagent (N,N-diethyl-2,3,3,3-tetrafluoropropionamide) were distilled off under reduced pressure, and the residue was applied to silica gel column chromatography (developing solvent; hexane:ethyl acetate=5:1 to 0:1) to give the titled compound (4.61 g, colorless oil).

1. customAfter the reaction
2. customseparated into organic and aqueous layers
3. extractionThe aqueous layer was extracted with ethyl acetate
4. customobtained above,
5. washwashed sequentially with 10% aqueous potassium bisulfate and saturated aqueous sodium chloride
6. dry with materialdried over anhydrous sodium sulfate
7. customAfter drying
8. distillationthe solvent and the decomposition product of Ishikawa reagent (N,N-diethyl-2,3,3,3-tetrafluoropropionamide) were distilled off under reduced pressure

ORD record

ord-e80dc711bd8b46728c95115c5d4b8b59

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07279584B2