3-Cyclohexyl-L-alanine → 2-(4-formylphenyl)-2-methylpropanenitrile

A suspension of lithium tris(dihexylamino)aluminum hydride, prepared according to Cha, J. S., et al; Org. Prep. Proc. Int. 1992, 24(3), 331-334, (21.2 g, 36 mmol) in THF (20 mL) was added via syringe to a solution of Example 35A (3.50 g, 20.6 mmol) in THF (50 mL) at 0° C. The reaction was allowed to proceed for 8 hr at 0° C., and then carefully quenched by addition of 3 N aq HCl(100 mL). The mixture was diluted with EtOAc, and the separated aqueous phase was extracted with EtOAc. The combined organic layer was washed with brine causing a white precipitate to form, which was filtered off. The filtrate was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting yellow solid was triturated with hexanes and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography (Analogix® Intelliflash 280; 5% to 25% EtOAc/hexanes eluant; SF40-115 g column) to yield 2.24 g (63%) of the title compound as a pale yellow oil. 1H NMR (300 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.00-7.93 (m, 2H), 7.80-7.74 (m, 2H), 1.73 (s, 6H). MS (DCI+) m/z 173 (M+).

1. customprepared
2. customcarefully quenched by addition of 3 N aq HCl(100 mL)
3. additionThe mixture was diluted with EtOAc
4. extractionthe separated aqueous phase was extracted with EtOAc
5. washThe combined organic layer was washed with brine causing a white precipitate
6. customto form
7. filtrationwhich was filtered off
8. dry with materialThe filtrate was dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe resulting yellow solid was triturated with hexanes
12. filtrationfiltered
13. concentrationThe filtrate was concentrated in vacuo
14. customthe residue was purified by flash chromatography (Analogix® Intelliflash 280

ORD record

ord-250cd4c187e14bfeabeb3e173305ee4f

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998993B2