Toluene → (2R,3R)-1-Benzyl 4-tert-butyl 3-(4-methylisoxazol-3-yl)-2-(3,3,3-trifluoropropyl)succinate

Temperature

-78 °C

To tert-butyl 2-(4-methylisoxazol-3-yl)acetate (25 mg, 0.127 mmol) (S7C) in a 10 mL round bottomed flask at room temperature was added THF (Ratio: 4.00, Volume: 0.8 mL). The solution was colorless. The solution was stirred at −78° C. 10 min. Next, 0.5 M KHMDS in toluene (0.317 mL, 0.158 mmol) was added slowly. The color of the solution turned to light orange. The mixture was stirred at −78° C. for 10 min and then placed in a room temperature water bath. After 10 minutes, the reaction mixture was put into a −78° C. bath for 20 min. (R)-Benzyl 5,5,5-trifluoro-2-(trifluoromethylsulfonyloxy)pentanoate, Intermediate S5D (65.0 mg, 0.165 mmol) in THF (Ratio: 1.000, Volume: 0.2 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 4 h. The reaction was quenched with saturated aqueous NH4Cl at −78° C. The mixture was placed in a room temperature water bath and diluted with brine. After 5 minutes, the mixture was extracted with EtOAc. The organic layer was separated and washed with brine, dried over MgSO4, filtered and concentrated to give a crude material as Intermediate S7D.

1. custom10 min
2. stirringThe mixture was stirred at −78° C. for 10 min
3. customplaced in a room temperature
4. customwas put into a −78° C.
5. customfor 20 min.
6. additionwas added dropwise
7. stirringThe reaction mixture was stirred at −78° C. for 4 h
8. customThe reaction was quenched with saturated aqueous NH4Cl at −78° C
9. customwas placed in a room temperature
10. additiondiluted with brine
11. waitAfter 5 minutes
12. extractionthe mixture was extracted with EtOAc
13. customThe organic layer was separated
14. washwashed with brine
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated

ORD record

ord-9caa662f253943159955d79fe9e4704f

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249157B2