Benzaldehyde → Mandelonitrile

Temperature

-78 °C

To a stirred solution of compound (II) (0.0897 g, 16.5 mol %) and molecular sieve 4 Å (powder, 65 mg, dehydrated under the condition of 0.3 mmHg/300° C. for 24 h before use) in dichloromethane (2.5 ml) was added titanium tetraisopropoxide (0.045 ml, 15 mol %) under argon at room temperature. Stir for 1 hour. Trimethylsilyl cyanide (0.15 ml, 1.1 mmol) was added to the reaction mixture and stirred for additional 0.5 h. Then, the reaction mixture was cooled to −78° C. and benzaldehyde (0.1 ml, 1 mmol) was added to the reaction mixture. The resultant reaction mixture was stirred for 48 h. The disappearance of the aldehyde was monitored by thin layer chromatography (ethyl acetate/hexane=1/5). The reaction mixture was quenched with 1 N HCl (10 ml) and stirred vigorously at room temperature for 6 h. After filtering, the mixture was extracted with dichloromethane (2×10 ml). The combined organic extracts were washed with brine (2×10 ml) and dried over anhydrous Na2SO4, then concentrated in vacuo. The residue was distilled under reduced pressure to afford 2-hydroxyl-2-phenylacetonitrile (87%, 93.2% e.e. (enantiomeric excess)). The result is listed in table 1.

1. stirringstirred for additional 0.5 h
2. customThe resultant reaction mixture
3. stirringwas stirred for 48 h
4. customThe reaction mixture was quenched with 1 N HCl (10 ml)
5. stirringstirred vigorously at room temperature for 6 h
6. filtrationAfter filtering
7. extractionthe mixture was extracted with dichloromethane (2×10 ml)
8. washThe combined organic extracts were washed with brine (2×10 ml)
9. dry with materialdried over anhydrous Na2SO4
10. concentrationconcentrated in vacuo
11. distillationThe residue was distilled under reduced pressure

ORD record

ord-1fb1a2a407824c4faefb8be45c672590

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06258966B1