2-Chloropropane → 2-(3,3-Diethoxypropyl)-2-(prop-2-yl)-2-(3,4-dimethoxyphenyl)acetonitrile

HRID 65298

Reaction equation

[CH2:1]([O:3][CH:4]([O:20][CH2:21][CH3:22])[CH2:5][CH2:6][CH:7]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)[C:8]#[N:9])[CH3:2].Cl[CH:24]([CH3:26])[CH3:25].IC(C)C.[H-].[Na+]>CN(C=O)C>[CH2:1]([O:3][CH:4]([O:20][CH2:21][CH3:22])[CH2:5][CH2:6][C:7]([CH:24]([CH3:26])[CH3:25])([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)[C:8]#[N:9])[CH3:2]

Participants

Conditions

Temperature: 40 °C

Procedure

The resulting acetal derivative of formula 5 is then alkylated with about 1 eq of an alkylhalide using a strong metallic base and a catalytic amount of an iodide source, e.g., 2-iodopropane or NaI, in a polar aprotic solvent at about 10°-40° C. for 2-18 hours, followed by treatment with sufficient ice water to decompose excess base, to yield a dialkylated derivative of formula 6. For example, 2-(3,3-diethoxypropyl)-2-(3,4-dimethoxyphenyl)acetonitrile (5) in DMF is treated with a slight molar excess of 2-chloropropane (and 0.1-5 mol% 2-iodopropane) at 20° C., stirred for 10 minutes, then treated with 1 eq NaH in mineral oil and slowly heated to 40° C. After adding 200 mL ice water and purifying the product, 2-(3,3-diethoxypropyl)-2-(prop-2-yl)-2-(3,4-dimethoxyphenyl)acetonitrile (6) is obtained.

Workup

customat 20° C.
custompurifying the product

Sources & evidence

ORD record: ord-c79bbfabb8f84ffab727a216b1ceab24
Source dataset: uspto-grants-1986_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04613606

Linked notes

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