Methyl iodide → 1-tert-Butyl 2-methyl (2S)-2-methylpyrrolidine-1,2-dicarboxylate

Temperature

78 °C

To a stirred solution of diisopropylamine (2.02 mL, 0.0144mol) in THF (30 mL) was added dropwise 1.59 M n-hexane solution of n-BuLi (9.06 mL, 0.0144mol) at minus 78° C. for over 5 min. The resulting solution was stirred for 20 min at minus 78° C. To the solution was added dropwise N-tert-butoxycarbonylproline methyl ester (3.00 g, 0.0131 mmol) in THF (30 mL) at minus 78° C. for over 5 min. The resulting solution was stirred for 10 min at minus 78° C. To the solution was added dropwise MeI (0.900 mL, 0.0144 mol) at minus 78° C. The resulting solution was stirred for 30 min at minus 78° C. The solution was quenched by the addition of sat. NH4Cl. The resulting mixture was extracted with CHCl3. The extract was washed with water, dried over Na2SO4, and evaporated in vacuo to afford 3.20 g (q.y.) N-tert-butoxycarbonyl-2-methylproline methyl ester as a yellow syrup. 1H-NMR (CDCl3) δ 1.33 (s, 9H), 1.38 (s, 3H), 1.72–2.20 (m, 4H) 3.27–3.59 (m, 2H) 3.63 (d, J=6.3 Hz, 3H).

1. stirringThe resulting solution was stirred for 10 min at minus 78° C
2. stirringThe resulting solution was stirred for 30 min at minus 78° C
3. customThe solution was quenched by the addition of sat. NH4Cl
4. extractionThe resulting mixture was extracted with CHCl3
5. washThe extract was washed with water
6. dry with materialdried over Na2SO4
7. customevaporated in vacuo

ORD record

ord-740fcd988c4e4f1188526ac444b53da9

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179819B2