Methyl iodide → (3R,7aS)-Tetrahydro-7a-methyl-3-(trichloromethyl)-1H,3H-pyrrolo[1,2-c]oxazol-1-one

Temperature

0 °C

n-Butyllithium (1.31 M, 4.68 cm3, 6.14 mmol) was added dropwise to a stirred solution of diisopropylamine (0.86 cm3, 6.14 mmol) in dry tetrahydrofuran (10 cm3) at −78° C. under an atmosphere of nitrogen. The solution was stirred for 5 min, warmed to 0° C. and stirred for 15 min. The solution was added dropwise to a solution of oxazolidinone 7 (1.00 g, 4.09 mmol) in dry tetrahydrofuran (20 cm3) at −78° C. over 20 min (reaction mixture turned dark), stirred for a further 30 min then iodomethane (0.76 cm3, 12.3 mmol) added dropwise over 5 min. The solution was warmed to −50° C. over 2 h. Water (15 cm3) was added, the solution warmed to room temperature and extracted with chloroform (3×40 cm3). The combined organic extracts were dried (MgSO4), filtered and evaporated to dryness in vacuo to give a dark brown semi-solid. Purification of the residue by flash column chromatography (15% ethyl acetate-hexane) afforded oxazolidinone 8 (0.67 g, 63%) as a pale yellow solid: mp 55-57° C. (lit. Wang 57-60° C.): δH (300 MHz; CDCl3) 1.53 (3H, s, CH3), 1.72-2.02 (3H, m, Proβ-H and Proγ-H2), 2.18-2.26 (1H, m, Proβ-H), 3.15-3.22 (1H, m, Proδ-H), 3.35-3.44 (1H, m, Proδ-H) and 4.99 (1H, s, NCH).

1. stirringstirred for 15 min
2. custom(reaction mixture turned dark)
3. stirringstirred for a further 30 min
4. temperatureThe solution was warmed to −50° C. over 2 h
5. temperaturethe solution warmed to room temperature
6. extractionextracted with chloroform (3×40 cm3)
7. dry with materialThe combined organic extracts were dried (MgSO4)
8. filtrationfiltered
9. customevaporated to dryness in vacuo
10. customto give a dark brown semi-solid
11. customPurification of the residue by flash column chromatography (15% ethyl acetate-hexane)

ORD record

ord-76f3eac54d0d41a889a2b356811b1a19

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863304B2