Diethyl (cyanomethyl)phosphonate → HCID 69202713, compound

HRID 2378174Notes

Reaction equation

HRID 2378174 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=3)=O)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.C(OP([CH2:31][C:32]#[N:33])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O1C2C=CC(C(C3C=C(OC)C=C(OC)C=3)=CC#N)=CC=2OCC1>C1COCC1>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=3)=[CH:31][C:32]#[N:33])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 692032153-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-3-(3,5-dimethoxyphenyl)acrylonitrileHCID 69203894HCID 69203894, compound

Product 1

HCID 69202713HCID 69202713, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2,3-dihydrobenzo[1,4]dioxin-6-yl)-(3,4-dimethoxyphenyl)methanone (3.01 g, 10.02 mmol), cyanomethylphosphonic acid diethyl ester (3.15 ml, 20.05 mmol) in anhydrous THF (20 ml), and lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 20.05 ml, 20.05 mmol) were treated in the same manner as described above for the synthesis of 3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-3-(3,5-dimethoxyphenyl)acrylonitrile. The crude material was purified via flash column chromatography (5% EtOAc in hexane gradient to 40% EtOAc in hexane in about 40 min.) to give an oil, which was lyophilized to give 3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-3-(3,4-dimethoxy-phenyl)-acrylonitrile as an light yellow foam (2.80 g, 86%): 1HNMR (DMSO-d6) δ 7.09-6.69 (m, 6H, Ar), 6.15 (s, 0.49H, double bond proton of one isomer), 6.09 (s, 0.45H, double bond proton of the other isomer), 4.33-4.25 (m, 4H, 2CH2CH2), 3.83-3.74 (multiple singlets, 2OCH3); 13C NMR (DMSO-d6) δ 161.0, 160.9, 150.9, 150.0, 148.6, 148.3, 145.6, 144.7, 143.2, 143.0, 131.3, 130.5, 130.1, 129.2, 122.6, 122.4, 122.3, 122.0, 118.7, 118.7, 118.0, 117.2, 117.1, 117.0, 112.7, 111.4, 111.2, 111.1, 93.1, 93.0, 64.3, 64.2, 64.0, 64.0, 55.6, 55.5. Anal. Calcd. For C19H17NO4 (+0.45H2O): C, 68.85; H, 5.44; N, 4.23. Found: C, 68.69; H, 5.31; N, 4.04.

Workup

  1. customThe crude material was purified via flash column chromatography (5% EtOAc in hexane gradient to 40% EtOAc in hexane in about 40 min.)
  2. customto give an oil, which

Sources & evidence

ORD record
ord-fef03dfac99b4275bd0f01f12e317c61
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

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