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

HRID 272928Notes

Reaction equation

COC([CH:5]1[CH2:10][C:9]([C:26]#[N:27])([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:13][CH:12]=2)[CH2:8][CH2:7][C:6]1=[O:28])=O.CS(C)=O.[Cl-].[Na+]>O>[O:28]=[C:6]1[CH2:5][CH2:10][C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:13][CH:12]=2)([C:26]#[N:27])[CH2:8][CH2:7]1

Participants

Conditions

Temperature: 144 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-0f4b878c363e410884e1726ae1ee49e2
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07456164B2

Reaction notes

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