Water → 3-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-3-(4-methoxy-phenyl)-acrylonitrile

HRID 2378303Notes

Reaction equation

HRID 2378303 reaction equation
C(OP([CH2:9][C:10]#[N:11])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:22]1[C:27]2[CH:28]=[CH:29][C:30]([C:32]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)=O)=[CH:31][C:26]=2[O:25][CH2:24][CH2:23]1.O>C1COCC1>[O:22]1[C:27]2[CH:28]=[CH:29][C:30]([C:32]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)=[CH:9][C:10]#[N:11])=[CH:31][C:26]=2[O:25][CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 962WaterHCID 75676Diethyl (cyanomethyl)phosphonateHCID 1519947STK163074HCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 692055283-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-3-(4-methoxy-phenyl)-acrylonitrileYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of cyanomethylphosphonic acid diethyl ester (2.4 mL, 15.0 mmol) in anhydrous THF (20 mL) was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 15.0 mL, 15.0 mmol) at 0° C. and stirred for 30 min at room temperature followed by addition of (2,3-dihydro-benzo[1,4]dioxin-6-yl)-(4-methoxy-phenyl)-methanone (2.02 g crude, 7.5 mmol) in THF (15 mL) and refluxed for 30 min. The reaction mixture was poured into water (50 if L), extracted with CH2Cl2 (2×50 mL). The combined organic phases were washed with brine (50 mL), dried over MgSO4, and purified via flash column chromatography (EtOAc, Hexane) to give 3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-3-(4-methoxy-phenyl)-acrylonitrile as a yellow solid (1.44 g, 66% yield): mp, 112-114° C.; 1H NMR (DMSO-d6) δ 3.79 and 3.83 (2s, 3H, OCH3), 4.25-4.33 (m, 4H, CH2CH2), 6.07 and 6.08 (2s, 1H, CH), 6.77-7.32 (m, 7H, Ar); 13C NMR (DMSO-d6) δ 55.2, 55.3, 64.0, 64.0, 64.2, 64.3, 92.7, 93.0, 113.9, 114.1, 117.0, 117.2, 118.0, 118.6, 118.7, 121.9, 122.5, 129.1, 130.0, 130.1, 130.4, 130.8, 131.4, 143.1, 143.2, 144.7, 145.5, 160.3, 160.7, 160.8, 161.1. Anal. Calcd for C18H15NO3+0.1H2O: C, 73.26; H, 5.19; N, 4.75. Found: C, 72.96; H, 5.22; N, 4.67.

Workup

  1. temperaturerefluxed for 30 min
  2. extractionextracted with CH2Cl2 (2×50 mL)
  3. washThe combined organic phases were washed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. custompurified via flash column chromatography (EtOAc, Hexane)

Sources & evidence

ORD record
ord-7a595c8527584bdcb6f8ec9ebf17e55a
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

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