Dimethyl Sulfoxide → 4-Oxo-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarbonitrile

To a solution of 5-cyano-2-oxo-5-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarboxylic acid methyl ester (6.6 g, 17 mmol) and dimethylsulfoxide (128 mL) was added water (8.0 mL) and sodium chloride (6.4 g, 109 mmol). The reaction mixture was heated to 142-146° C. After 5 hr, the mixture was concentrated and the residue was dissolved in DCM (120 mL), washed with water (100 mL), and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (70 g silica gel, eluant:gradient of DCM/MeOH 95/5 to 90/10) providing 4-oxo-1-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexanecarbonitrile as a crystallizing oil (2.2 g, 45.5%). After crystallization in ether, 0.2 g of analytical sample were obtained. 1H NMR (400 MHz, CDCl3) δ7.32 (d, 2H), 6.88 (d, 2H), 4.1 (t, 2H), 2.95-2.8 (m, 2H), 2.65-2.38 (m, 10H), 2.3-2.15 (m, 2H), 2.0-1.9 (m, 2H), 1.8-1.7 (m, 4H).

1. concentrationthe mixture was concentrated
2. dissolutionthe residue was dissolved in DCM (120 mL)
3. washwashed with water (100 mL), and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by flash chromatography (70 g silica gel, eluant:gradient of DCM/MeOH 95/5 to 90/10)

ORD record

ord-0f4b878c363e410884e1726ae1ee49e2

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456164B2