Benzaldehyde → (S)-(-)-1-Benzyl-3-pyrrolidinol

A solution of (3S)-3-hydroxypyrrolidine (2.0 g, 25 mmol) 50 mL CH2Cl2, under a nitrogen atmosphere, was cooled to 0° C. and benzaldehyde (2.92 g, 27.5 mmol was added, followed by 1 g of powdered 4A molecular sieves. Sodium triacetoxyborohydride (7.4 gm, 35 mmol)was added in several portions over 30 min, and the reaction was allowed to stir at room temperature for 18 h. The reaction was again cooled to 0° C. and quenched by addition of 10 mL methanol, followed by 5 mL of 1N HCl. The molecular sieve solids were removed by filtration through a glass fiber paper, and the filtrate was extracted with 20 mL diethyl ether. The organic phase was discarded, and the aqueous phase was first basified by addition of conc. ammonium hydroxide, and then extracted with EtOAc (3×20 mL). The combined extracts were washed with 20 mL brine, dried (MgSO4), filtered, and concentrated in vacuo to furnish 3.2 g (73%) of clear yellow oil, which required no further purification. 1H-NMR (400 MHz, CDCl3) δ7.2-7.4 (m, 5H), 4.33 (, 11H), 3.63, (s, 2H), 2.83-3.89 (m, 1H), 2.67 (d, J=9.9 Hz, 1H), 2.53-2.55 (m, 1H), 2.23-2.34 (m, 1H), 2.14-2.20 (m, 2H), 1.70-1.77 (n, 11H).

1. temperatureThe reaction was again cooled to 0° C.
2. customquenched by addition of 10 mL methanol
3. customThe molecular sieve solids were removed by filtration through a glass fiber paper
4. extractionthe filtrate was extracted with 20 mL diethyl ether
5. additionthe aqueous phase was first basified by addition of conc. ammonium hydroxide
6. extractionextracted with EtOAc (3×20 mL)
7. washThe combined extracts were washed with 20 mL brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-9eabff94dae6416f9ee1bc35a1d58fa1

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067506B2