1-Naphthaleneacetonitrile → (1S)-2-Hydroxymethyl-1-(1-naphthyl)-cyclopropanecarbonitrile

Temperature

-15 °C

1-Naphthylacetonitrile (30 g, 180 mmole) was dissolved in dry tetrahydrofuran (THF, 300 mL) under nitrogen atmosphere, cooled to −15° C. and sodium-bis (trimethylsilylamide) in 1M tetrahydrofuran (180 mL) was added dropwise. The resulting brown mixture was stirred for 45 min at −10° C. to 0° C., cooled to −15° C. and added a solution of R-(+) epichlorohydrin (16.6 g, 180 mmol) in tetrahydrofuran (20 mL) was added dropwise at −15° C. and stirred for 30 min. Sodiumbis (trimethylsilylamide) in 1M tetrahydrofuran (180 mL) is added drop wise at −15° C. and the mixture was stirred for 45 min. The temperature of the reaction mass was then gradually raised to room temperature and maintained at room temperature for 30 min. The reaction is monitored by TLC (ethyl acetate/hexane (1:1)). The reaction mass was quenched with water (80 mL). The aqueous layer was extracted with ethyl acetate (2×75 mL). The combined organic layer was washed with brine solution (200 mL), dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to yield 55 g of crude oil. The oil was purified by column chromatography (silica gel, ethyl acetate/hexane (10:90) to yield 25 g (62%) of product. The 1H NMR shows mixture of diasteromers (2:1 cis/trans). 1H NMR δ(300 MHz,CDCl3, partial assignment): 1.55-1.59 (2H,m), 1.94-2.04 (1H,m), 2.42 (1H,m) 3.08 (1H,br,s), 3.32 (1H,m),7.42-7.68 (4H,m),7.72-7.93 (2H,m),8.37-8.40 (1H,d,J=8.4 Hz).

1. temperaturecooled to −15° C.
2. additionwas added dropwise at −15° C.
3. stirringstirred for 30 min
4. stirringthe mixture was stirred for 45 min
5. temperatureThe temperature of the reaction mass was then gradually raised to room temperature
6. temperaturemaintained at room temperature for 30 min
7. customThe reaction mass was quenched with water (80 mL)
8. extractionThe aqueous layer was extracted with ethyl acetate (2×75 mL)
9. washThe combined organic layer was washed with brine solution (200 mL)
10. dry with materialdried over anhydrous sodium sulphate
11. filtrationfiltered
12. customevaporated under reduced pressure
13. customto yield 55 g of crude oil
14. customThe oil was purified by column chromatography (silica gel, ethyl acetate/hexane (10:90)

ORD record

ord-0313e17fb35f45a687786691bae08379

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138377B2