Sodium Iodide → 4-{4,4-Dimethyl-2,5-dioxo-3-[3-(tetrahydro-furan-2-yloxy)-propyl]-imidazolidin-1-yl}-2-trifluoromethyl-benzonitrile

HRID 1919299Notes

Reaction equation

[CH3:1][C:2]1([CH3:21])[C:6](=[O:7])[N:5]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=2)[C:4](=[O:20])[NH:3]1.[H-].[Na+].ClC[CH2:26][CH2:27][O:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][O:30]1.[I-].[Na+]>CN(C=O)C.C(OCC)C>[CH3:1][C:2]1([CH3:21])[C:6](=[O:7])[N:5]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([C:16]([F:19])([F:17])[F:18])[CH:9]=2)[C:4](=[O:20])[N:3]1[CH2:33][CH2:32][CH2:31][O:30][CH:29]1[CH2:34][CH2:26][CH2:27][O:28]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of compound 11a (950 mg, 3.20 mmol) in anhydrous DMF (10 mL) under argon at room temperature was carefully added sodium hydride (60% suspension in oil) (140 mg, 3.50 mmol). The solution was stirred for 30 min and 2-(3-chloropropoxy)-tetrahydro-2H-pyran (656 mg, 3.66 mmol) was dropwise added. Finally, sodium iodide (480 mg, 3.20 mmol) was added and the solution was heated at 50° C. for 36 hrs. The resulting solution was diluted with diethyl ether (75 mL), washed successively with a 10% potassium phosphate and brine solution, and finally dried with magnesium sulphate. The crude compound was purified by flash chromatography using EtOAc/Hexane (3:7) as an eluant to give pure compound 12a (1.03 g, 73%). 1H NMR (300 MHz, Acetone-d6) δ: 1.51 (m, 4H), 1.57 (s, 6H), 1.6-1.9 (m, 2H), 2.04 (m, 2H), 3.50 (m, 4H), 3.80 (m, 2H), 4.59 (t, 1H, J=3.42 Hz), 8.18 (m, 2H), 8.27 (s, 1H).

Workup

customat room temperature
washwashed successively with a 10% potassium phosphate and brine solution
dry with materialfinally dried with magnesium sulphate
customThe crude compound was purified by flash chromatography

Sources & evidence

ORD record: ord-2d68532ea1324032b56eba2ec1e4043f
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168627B2

Reaction notes

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