Toluene → (3R,4R)-1-Benzylpyrrolidine-3,4-diol

To a mechanically stirred and cooled solution (0° C.) of the product from Step 1 (50 g, 0.23 mol) in dry THF (1.24 L) was added sodium aluminum hydride bis-(methoxyethoxide) (289 mL of a 65% Red-A;®/Toluene solution, 0.95 mol) under a nitrogen atmosphere at such a rate that the internal temperature did not exceed 20° C. The reaction mixture was allowed stir at room temperature for 2 h after the addition was complete. The reaction mixture was slowly poured into ice water (1.0 L) with stirring to quench the reaction. After warming to room temperature, 30% ammonium hydroxide (100 mL) was added followed by EtOAc (1.5 L) and this mixture was stirred for 16 h. The suspension was filtered through diatomaceous earth and the solids were washed with EtOAc. The filtrate layers were separated and the organic phase was dried over sodium sulfate and concentrated to afford a syrup. Dissolution in dichloromethane and concentration affords a white solid that is collected and dried (43.7 g, 86%). 1H NMR (400 MHz, CDCl3) δ 7.36-7.23 (5H, m), 6.23 (2H, m), 4.65 (1H, m), 4.15-4.00 (3H, m), 3.62-3.49 (1H, dd), 3.33 (1H, dd), 3.14 (1H, dd), 2.94 (1H dd). MS m/z 194 (MH+).

1. customdid not exceed 20° C
2. stirringThe reaction mixture was allowed stir at room temperature for 2 h
3. additionafter the addition
4. stirringwith stirring
5. customto quench
6. customthe reaction
7. stirringthis mixture was stirred for 16 h
8. filtrationThe suspension was filtered through diatomaceous earth
9. washthe solids were washed with EtOAc
10. customThe filtrate layers were separated
11. dry with materialthe organic phase was dried over sodium sulfate
12. concentrationconcentrated
13. customto afford a syrup
14. concentrationconcentration
15. customaffords a white solid
16. customthat is collected
17. customdried (43.7 g, 86%)

ORD record

ord-b7df049199fa474d9a4761a2a2b71f4e

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07485641B2