Hydrochloric Acid → [(2R)-5-Oxopyrrolidin-2-yl]methyl 4-methylbenzene-1-sulfonate

To a mixture of (R)-ethyl 5-oxopyrrolidin-2-carboxylate (Aldrich, 3 g, 19 mmol) and sodium borohydride (1.89 g, 50 mmol) in tetrahydrofuran (30 mL) at 50° C. was added dropwise for 30 min methanol (10 mL). The reaction was then continued for an additional 15 min and cooled to room temperature. The mixture was treated with 1N HCl to pH=3 and concentrated under reduced pressure. The residue was triturated with anhydrous methanol and the solid was filtered off and washed with methanol. The filtrate and washings were combined and concentrated under reduced pressure. The concentrate was then triturated with anhydrous tetrahydrofuran and filtered. The filtrate was concentrated under reduced pressure and the concentrate was dissolved in anhydrous CH2Cl2 (20 mL). p-Toluenesulfonyl chloride (3.64 g, 19 mmol) was added, the mixture was cooled to 0° C. and triethylamine (2.66 mL, 19 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 12 h. The mixture was then washed with water, brine, dried with anhydrous MgSO4 and concentrated under reduced pressure. The residue was chromatographed (SiO2, ethyl acetate-ethanol 9:1) to afford 3.5 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 1.62 (m 1H), 2.06 (m, 3H), 2.42 (s, 3H), 3.71 (m, 1H), 3.87 (dd, J=10 Hz, 4 Hz, 1H), 3.97 (dd, J=10 Hz, 4 Hz, 1H), 7.49 (d, J=9 Hz, 2H), 7.75 (broad s, 1H), 7.82 (d, J=9 Hz, 2H); MS (DCI/NH3) m/z 270 (M+H)+, 287 (M+NH4)+.

1. concentrationconcentrated under reduced pressure
2. customThe residue was triturated with anhydrous methanol
3. filtrationthe solid was filtered off
4. washwashed with methanol
5. concentrationconcentrated under reduced pressure
6. customThe concentrate was then triturated with anhydrous tetrahydrofuran
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under reduced pressure
9. dissolutionthe concentrate was dissolved in anhydrous CH2Cl2 (20 mL)
10. temperaturethe mixture was cooled to 0° C.
11. temperatureto warm to room temperature
12. washThe mixture was then washed with water, brine
13. dry with materialdried with anhydrous MgSO4
14. concentrationconcentrated under reduced pressure
15. customThe residue was chromatographed (SiO2, ethyl acetate-ethanol 9:1)

ORD-Eintrag

ord-ac618bf57a224654840eb2ef78158b03

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08058293B2