tert-Butyl acrylate → (S)-tert-butyl 4-((R)-5-tert-butoxy-2-((R)-4-methyl-2-oxooxazolidine-3-carbonyl)-5-oxopentyl)-2,2-dimethyloxazolidine-3-carboxylate

At 0° C., 1.0M TiCl4 in CH2Cl2 solution (8.55 mL, 0.7 eq) was added to CH2Cl2 (100 mL) followed by the addition of 1.0M TiCl(Oi-Pr)3 in hexanes solution (4.28 mL, 0.35 eq) and stirred 5 min DIPEA (2.87 mL, 1.35 eq) was added and stirred 15 min. A solution of (S)-tert-butyl 2,2-dimethyl-4-(3-((R)-4-methyl-2-oxooxazolidin-3-yl)-3-oxopropyl)oxazolidine-3-carboxylate (5.28 g, 12.22 mmol) in CH2Cl2 (50 mL) was added. The reaction mixture was stirred 1 hr at 0° C. To the solution, t-butylacrylate (2.22 mL, 1.25 eq) was added and the mixture was left stirred over 48 hr with concomitant warming to rt. The mixture was concentrated, partitioned between EtOAc (300 mL) and 1% HCl solution (100 mL). The organic layer was washed with sat. NaHCO3 solution (60 mL), brine (60 mL), dried over Na2SO4. After filtration and concentration, the residue was purified by ISCO (120 g column, 0→35% EtOAc in Hexanes gradient) to afford 4.12 g (60%) (S)-tert-butyl 4-((R)-5-tert-butoxy-2-((R)-4-methyl-2-oxooxazolidine-3-carbonyl)-5-oxopentyl)-2,2-dimethyloxazolidine-3-carboxylate as a yellowish solid. MS ESI +ve m/z 583 (M+Na).

1. additionwas added
2. stirringThe reaction mixture was stirred 1 hr at 0° C
3. waitthe mixture was left
4. stirringstirred over 48 hr
5. concentrationThe mixture was concentrated
6. custompartitioned between EtOAc (300 mL) and 1% HCl solution (100 mL)
7. washThe organic layer was washed with sat. NaHCO3 solution (60 mL), brine (60 mL)
8. dry with materialdried over Na2SO4
9. filtrationAfter filtration and concentration
10. customthe residue was purified by ISCO (120 g column, 0→35% EtOAc in Hexanes gradient)

ORD record

ord-133dfac43c6f48fe8b82566cb88e6012

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487108B2