Diisobutylaluminum hydride → HCID 66845535, compound

Temperature

-78 °C

tert-Butyl 2,2-dimethyl-5-oxopyrrolidine-1-carboxylate (1.17 g, 5.49 mmol) was dissolved in Et2O (15 mL) and cooled to −78° C. The solution was treated with DIBAL-H (3.73 mL, 5.60 mmol). The mixture was stirred at −78° C. for 2 hours and then warmed to ambient temperature overnight. The reaction was quenched by addition of an aliquot (7 mL) of a solution of p-toluenesulfonic acid hydrate (0.012 g) in MeOH (12 mL). The mixture was stirred at ambient temperature for 60 hours. The suspension was concentrated in vacuo and re-suspended in a mixture of Rochelle's salt (0.5N) and ethyl acetate. After separation, the aqueous portion was washed with ethyl acetate (2×). The combined organics were then washed with saturated NaCl, dried over Na3SO4 and concentrated in vacuo to an oil (92%). A solution of titanium(IV) chloride (3.71 mL, 3.71 mmol) in toluene was cooled to 0° C. and treated with a solution of (R)-4-benzyl-3-(2-(4-chlorophenyl)acetyl)oxazolidin-2-one (1.11 g, 3.38 mmol) dissolved in dichloromethane (7 mL). After 5 minutes, diisopropylethylamine (0.647 mL, 3.71 mmol) was added. The resultant solution was stirred for 1 hour at 0° C. and then cooled to −20° C. A solution of tert-butyl 5-hydroxy-2,2-dimethylpyrrolidine-1-carboxylate (1.09 g, 5.06 mmol) in dichloromethane (7 mL) was added, and the mixture was stirred at −20° C. for 75 minutes. The reaction was quenched with saturated NH4Cl (about 4 mL) and diluted with water to dissolve the solids. After separation, the aqueous portion was washed with methylene chloride (3×). The combined organics were washed with water (2×), dried over Na3SO4 and concentrated in vacuo. The crude product was subjected to chromatography on SiO2 and eluted with 9:1 hexanes/ethyl acetate to produce (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (1.62 g, 61%). MS (ESI+) [M+H] 526.7/528.8.

1. temperaturewarmed to ambient temperature overnight
2. customThe reaction was quenched by addition of an aliquot (7 mL) of a solution of p-toluenesulfonic acid hydrate (0.012 g) in MeOH (12 mL)
3. stirringThe mixture was stirred at ambient temperature for 60 hours
4. concentrationThe suspension was concentrated in vacuo
5. additionre-suspended in a mixture of Rochelle's salt (0.5N) and ethyl acetate
6. customAfter separation
7. washthe aqueous portion was washed with ethyl acetate (2×)
8. washThe combined organics were then washed with saturated NaCl
9. dry with materialdried over Na3SO4
10. concentrationconcentrated in vacuo to an oil (92%)
11. waitAfter 5 minutes
12. temperaturecooled to −20° C
13. stirringthe mixture was stirred at −20° C. for 75 minutes
14. customThe reaction was quenched with saturated NH4Cl (about 4 mL)
15. additiondiluted with water
16. dissolutionto dissolve the solids
17. customAfter separation
18. washthe aqueous portion was washed with methylene chloride (3×)
19. washThe combined organics were washed with water (2×)
20. dry with materialdried over Na3SO4
21. concentrationconcentrated in vacuo
22. washeluted with 9:1 hexanes/ethyl acetate

ORD record

ord-8f77c27639364c6f9167e6ab555d202d

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372842B2