Water → HCID 58743044, compound

Lithium aluminum hydride (96 mL of 1.0 M solution in ether, 0.096 moles) was added to a cold (ice bath) solution of (3R)-1-[(1S)-2-hydroxy-1-methylethyl]-3-methylpyrrolidine-2,5-dione (8.26 g, 0.048 moles) in anhydrous ether (565 mL). The cold bath was removed and the resulting mixture was stirred at room temperature for 17 hours. The resulting mixture was cooled in an ice bath as water (3.7 mL) was added slowly dropwise (CALIMON: vigorous reaction, gas evolution) followed by 15% NaOH (3.7 mL) and additional water (11.0 mL). The resulting mixture was stirred vigorously for 15 minutes then sonicated for 15 minutes and filtered. The collected solid was washed with ether (2×125 mL; stirred vigorously for 15 minutes then sonicated 15 minutes and filtered) and the combined filtrates were dried (MgSO4), filtered, and evaporated to a light yellow oil (5.76 g). The crude product was purified by flash chromatography on silica gel (65×222 mm column) eluted with 10:7:2:1 ethyl acetate:hexane:methanol:triethylamine collecting 50 mL fractions after a forerun of 750 mL to afford the pure product (in fractions 6–50) as a light yellow liquid. 1H NMR: (CDCl3, 600 M) δ 3.54 & 3.32 (2H, 2 dd, J=5, 10 Hz, H1), 3.30 (1H, br s, OH), 2.83 & 2.11 (2H, 2 dd, J=8, 8 Hz, H2′), 2.62–2.67 & 2.54–2.59 (2H, 2m, H5′), 2.65–2.68 (2H, m, H2), 2.15–2.24 (1H, m, H3′), 1.92–1.98 & 1.28–1.34 (2H, 2m, H4′), 1.00 (6H, d, J=7 Hz, 2CH3s); 13C NMR: (CDCl3, 150 MHz) δ 64.54, 58.02, 57.46, 48.87, 32.45, 31.67, 20.24, 12.49; MS (electrospray): m/e 144 (M+H). [α]D−0.5° (c=1.0 in MeOH).

1. customThe cold bath was removed
2. temperatureThe resulting mixture was cooled in an ice bath as water (3.7 mL)
3. additionwas added slowly dropwise
4. custom(CALIMON: vigorous reaction, gas evolution)
5. stirringThe resulting mixture was stirred vigorously for 15 minutes
6. customthen sonicated for 15 minutes
7. filtrationfiltered
8. washThe collected solid was washed with ether (2×125 mL
9. stirringstirred vigorously for 15 minutes
10. customthen sonicated 15 minutes
11. filtrationfiltered) and the combined filtrates
12. dry with materialwere dried (MgSO4)
13. filtrationfiltered
14. customevaporated to a light yellow oil (5.76 g)
15. customThe crude product was purified by flash chromatography on silica gel (65×222 mm column)
16. washeluted with 10:7:2:1 ethyl acetate
17. customhexane:methanol:triethylamine collecting 50 mL fractions after a forerun of 750 mL to afford the pure product (in fractions 6–50) as a light yellow liquid

ORD record

ord-6b295db0fae345b593656deec65f1319

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07138426B2