Diethyl (cyanomethyl)phosphonate → 3-(3,5-Dimethoxy-phenyl)-3-(2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxin-5-yl)-acrylonitrile

HRID 970986Notes

Reaction equation

HRID 970986 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:13]2[C:22]3[O:21][C:20]([F:24])([F:23])[C:19]([F:26])([F:25])[O:18][C:17]=3[CH:16]=[CH:15][CH:14]=2)=O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(OP([CH2:35][C:36]#[N:37])(=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>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:13]2[C:22]3[O:21][C:20]([F:24])([F:23])[C:19]([F:26])([F:25])[O:18][C:17]=3[CH:16]=[CH:15][CH:14]=2)=[CH:35][C:36]#[N:37])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=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 86596006(3,5-Dimethoxyphenyl)-(2,2,3,3-tetrafluoro-2,3-dihydrobenzo[1,4]dioxin-5-yl)methanone

Product 1

HCID 851471773-(3,5-Dimethoxy-phenyl)-3-(2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxin-5-yl)-acrylonitrileYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3,5-Dimethoxyphenyl)-(2,2,3,3-tetrafluoro-2,3-dihydrobenzo[1,4]dioxin-5-yl)methanone (0.42 g, 1.13 mmol), cyanomethylphosphonic acid diethyl ester (0.36 ml, 2.26 mmol) in anhydrous THF (10 ml), and lithium bis (trimethylsilyl)amide (1.0 M solution in THF, 2.26 ml, 2.26 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 25% EtOAc in hexane in about 30 min.) to give 3-(3,5-dimethoxy-phenyl)-3-(2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxin-5-yl)-acrylonitrile as an oil (0.42 g, 94%): 1HNMR (DMSO-d6) 7.70-7.35 (m, 6H, Ar), 6.86 (s, 0.32H, double bond proton of one isomer), 6.68-6.66 (m, 2H, Ar), 6.53 (d, J=2 Hz, 1.3H, Ar), 6.48 (d, J=1 Hz, 0.7H, Ar), 6.27 (s, 0.62H, double bond proton of the other isomer), 3.74 (s, 6H, 2OCH3); 13C NMR (DMSO-d6) δ 160.7, 160.5, 155.0, 153.8, 138.0, 137.3, 136.7, 133.7, 128.7, 128.7, 127.8, 127.5, 126.8, 126.7, 126.5, 119.5, 119.3, 117.1, 116.9, 106.2, 105.3, 102.5, 101.8, 101.1, 100.6, 55.4, 55.4; Anal. Calcd. For C19H13F4NO4: C, 57.73; H, 3.31; N, 3.54; F, 19.22. Found: C, 57.62; H, 3.34; N, 3.49; F, 19.17.

Workup

  1. customThe crude material was purified via flash column chromatography (5% EtOAc in hexane gradient to 25% EtOAc in hexane in about 30 min.)

Sources & evidence

ORD record
ord-a979db6305ad4388a469f3c222c0c58a
Source dataset
uspto-grants-2007_12
Patent number
US07312241B2

Reaction notes

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