Diethyl Ether → benzyl[(2S)-1-{[tert-butyl(diphenyl)silyl]oxy}-5-fluoro-6-oxohexan-2-yl](3-methylbutyl)carbamate

Temperature

-20 °C

Racemic 5-benzyl-2-2,3-trimethylimidazolidin-4-one dichloroacetic acid (109 mg, 0.314 mmol) and N-fluorobenzenesulfonimide (593 mg, 1.88 mmol) were dissolved in 10% i-PrOH-THF (3.75 mL). The reaction mixture was cooled to −20° C., and the compound from Step 7 (900 mg, 1.57 mmol) in 1.25 mL of 10% i-PrOH-THF was added. The reaction mixture was stirred at −20° C. for 24 hours, 2 volumes of ether were added, and the resulting mixture was vigorously stirred, filtered through Davisil® silica (W.R. Grace & Co.-Conn.), and eluted with ether. 5 mL of methyl sulfide was added to the eluted reaction mixture. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to afford the title compound which was used directly at Step 9. 1H NMR (DMSO-d6): δ7.66-7.52 (m, 5H), 7.51-7.25 (m, 10H), 5.08 (s, 2H), 4.90-4.83 (m, 1H), 3.70-3.55 (m, 1H), 3.53-3.36 (m, 2H), 3.17-2.99 (m, 2H), 1.63-1.32 (m, 7H), 0.96 (s, 9H), 0.88-0.72 (m 6H), aldehyde signal missing due to hydrate form.

1. stirringthe resulting mixture was vigorously stirred
2. filtrationfiltered through Davisil® silica (W.R. Grace & Co.-Conn.)
3. washeluted with ether
4. addition5 mL of methyl sulfide was added to the eluted reaction mixture
5. customThe reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3
6. extractionextracted with EtOAc (2×)
7. washThe combined organics were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-2cd5724d397a4c03bac236b2269040ef

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09079834B2