Sodium hydride → (2S,4S)-1-(Benzyloxycarbonyl)-4-(2,2-difluoroethoxy)pyrrolidine-2-carboxylic acid

To a solution of (2S,4S)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (5.0 g, 18.85 mmol) in THF (100 mL) was added NaH (1.583 g, 39.6 mmol) at 0° C. under N2. The resulting suspension was stirred at RT for 30 min. A solution of 1,1-difluoro-2-(trifluoromethylsulfonyl)ethane (4.11 g, 20.73 mmol) in THF (5 ml) was added to the suspension. The reaction mixture was stirred at RT for 3 h. The reaction mixture was quenched with water and concentrated. The residue was extracted with EtOAc; the aqueous layers was acidified to ph 3 with 1N HCl and extracted with EtOAc. The organic layers were washed with water and brine, dried over Na2SO4, and filtered. The crude product was used in the next step without purification. LC/MS [M−H]+: 328; Ret time (Method F): 0.93 min (Phenomenex-Luna s10 4.6×50 mm column, 4 min gradient, 4 mL/min).

1. stirringThe reaction mixture was stirred at RT for 3 h
2. customThe reaction mixture was quenched with water
3. concentrationconcentrated
4. extractionThe residue was extracted with EtOAc
5. extractionextracted with EtOAc
6. washThe organic layers were washed with water and brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customThe crude product was used in the next step without purification
10. custom0.93 min (Phenomenex-Luna s10 4.6×50 mm column, 4 min gradient, 4 mL/min)

ORDレコード

ord-0164ecd3a2e74145a500b8a25cf26140

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08415340B2