Potassium Carbonate → (2S,3'S)-2-Methyl-[1,3]bipyrrolidinyl-1'-carboxylic acid tert-butyl ester

온도

75 °C

(R)-3-(Toluene-4-sulfonyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (52 g, 0.15 mol, 1.0 eq) prepared in accordance of the procedures set forth in Intermediate (i), (2S)-2-methyl pyrrolidine (25.2 g, 0.3 mol, 2.0 eq), anhydrous CH3CN (500 ml), and dry K2CO3 powder (50 g, 36 mmol, 2.4 eq) were added to a 2 L round-bottom flask equipped with a mechanical stirrer and a reflux condenser. The resulting suspension was stirred at 75° C. for 2 h. The heating block was set at 88° C. LC/MS showed a trivial amount of starting material at m/z 363. The reaction mixture was concentrated in vacuo. The residue was partitioned between 200 ml of water and 400 ml of DCM. The aqueous layer was washed with 50 ml of DCM twice. The organic extracts were combined and washed with 150 ml of saturated NaHCO3 solution, 150 ml of brine, and dried over K2CO3. The crude was purified by silica gel column, eluted with 5-10% MeOH in DCM. The product still had weak UV absorptions at 254 nm and 280 nm. A pale yellow oil was obtained, yield: 24.5 g (64%).

1. additionwere added to a 2 L round-bottom flask
2. customequipped with a mechanical stirrer and a reflux condenser
3. customwas set at 88° C
4. concentrationThe reaction mixture was concentrated in vacuo
5. customThe residue was partitioned between 200 ml of water and 400 ml of DCM
6. washThe aqueous layer was washed with 50 ml of DCM twice
7. washwashed with 150 ml of saturated NaHCO3 solution, 150 ml of brine
8. dry with materialdried over K2CO3
9. customThe crude was purified by silica gel column
10. washeluted with 5-10% MeOH in DCM
11. customA pale yellow oil was obtained

ORD 기록

ord-fa21d12cb64a4809bcb8600b94a62286

출처 데이터셋

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08623877B2