(1,6,7,8-tetrahydro-2H-indeno [5,4-b]furan-8-yl)acetonitrile

(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-ylidene)acetonitrile of formula (10):

enantioselective reduction on the intermediate of formula (10) to obtain (1,6,7,8-tetrahydro-2H-indeno [5,4-b]furan-8-yl)acetonitrile of formula (XI)

http://www.google.com/patents/US8242291
EXAMPLE 8

This example refers to reaction i of the process of the invention.

The product of formula (X) obtained as described in example 7 is dissolved in 22 kg of THF at room temperature. 2.8 kg of tetrabutylammonium fluoride trihydrate are added to the solution ensuring that the temperature does not exceed 30° C. (slight exothermia). It is kept under agitation for at least one hour at T=25±5° C. monitoring the progress of the reaction (TLC).

In a separate reactor a solution of 9 kg of NaCl in 45 l of water is prepared. At the end of the reaction the solution of NaCl is poured onto the reaction solution regulating the temperature so that it does not exceed 30° C. It is agitated for a few minutes and then re-extracted twice with 18 kg of isopropyl acetate. The collected organic phases are washed twice with 30 kg of water. The organic phase is concentrated to dryness distilling the solvent at a reduced pressure and T=45±5° C. 2.40 kg of oily residue are obtained which is purified by chromatography on 40 kg of silica gel (heptane:ethyl acetate 85:15). After elimination of the solvent at reduced pressure and T=45±5° C., 934 g of intermediate (XI) is obtained which is refluxed in 2.8 l of methanol in the presence of decolouring carbon. The suspension is hot filtered. Part of the solvent is distilled at reduced pressure until a residual volume of approximately 2.4 l is obtained. It is cooled to 0<T<5° C. for approximately 2 hours before filtering the solid. The product is dried at T=45° C. and at reduced pressure for approximately 12 hours. 577 g of intermediate (XI) are obtained of quality suitable for continuation of the synthesis. A sample of the product thus obtained, after further chromatographic purification for analytical purposes, undergoes ¹H-NMR and mass analysis obtaining the following result:

Electronic impact mass: [M⁺]=199; [M⁺]−CH₂CN=159

¹H-NMR (500 MHz, CDCl₃): δ (ppm)

1.98-2.08 ppm, m, 1H, 2.40-2.50 ppm, m, 1H, 2.52-2.59 ppm, dd, J=8 Hz, J=15 Hz, 1H, 2.66-2.75 ppm, dd, J=6 Hz, J=15 Hz, 1H, 2.81-2.88 ppm, m, 1H, 2.96-3.04 ppm, m, 1H; 3.13-3.22 ppm, m, 1H, 3.28-3.36 ppm, 1H, m; 3.48-3.56 ppm, m, 1H, 4.52-4.69 ppm, m, 2H, 6.69 ppm, d, J=8 Hz, 1H, 7.02 ppm, d, J=8 Hz, 1H.