Diethyl (cyanomethyl)phosphonate → 3-(3-Benzyloxyphenyl)-3-(3,5-dimethoxyphenyl)acrylonitrile

HRID 2378196Notes

Reaction equation

HRID 2378196 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]([C:17]2[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[C:19]([O:25][CH3:26])[CH:18]=2)=O)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]([C:17]2[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[C:19]([O:25][CH3:26])[CH:18]=2)=[CH:35][C:36]#[N:37])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 2733832Lithium HexamethyldisilazideHCID 69203059(3-Benzyloxyphenyl)-(3,5-dimethoxyphenyl)methanoneHCID 692032153-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-3-(3,5-dimethoxyphenyl)acrylonitrile

Product 1

HCID 692025963-(3-Benzyloxyphenyl)-3-(3,5-dimethoxyphenyl)acrylonitrileYield 86.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3-Benzyloxyphenyl)-(3,5-dimethoxyphenyl)methanone (10.66 g, 30.60 mmol), cyanomethylphosphonic acid diethyl ester (9.63 ml, 61.19 mmol) in anhydrous THF (10 ml), and lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 61.20 ml, 61.19 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 30% EtOAc in hexane in about 40 min.) to give 3-(3-benzyloxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile as a white solid (9.82 g, 86%): 1HNMR (DMSO-d6) 7.47-7.31 (m, 6H, Ar), 7.20-6.88 (m, 3H, Ar), 6.66-6.62 (2ts, 1H, Ar), 6.46 (d, J=2 Hz, 2H, Ar), 6.40 (s, 0.5H, double bond proton of one isomer), 6.38 (s, 0.5H, double bond proton of the other isomer), 5.12 (s, 1H, half CH2), 5.11 (s, 1H, half CH2), 3.76 (s, 3H, OCH3), 3.73 (s, 3H, OCH3); 13C NMR (DMSO-d6) δ 161.2, 160.4, 158.4, 158.2, 139.6, 138.9, 138.8, 138.3, 136.7, 129.8, 128.4, 127.9, 127.8, 121.5, 120.8, 117.9, 117.9, 116.8, 116.0, 115.5, 114.4, 107.1, 106.5, 101.9, 101.1, 96.8, 96.5, 69.4, 55.4, 53.6; Anal. Calcd. For C24H21NO3: C, 77.61; H, 5.70; N, 3.77. Found: C, 77.39; H, 5.70; N, 3.69.

Workup

  1. customThe crude material was purified via flash column chromatography (5% EtOAc in hexane gradient to 30% EtOAc in hexane in about 40 min.)

Sources & evidence

ORD record
ord-2b930427858646fa84d19a011cb17c5b
Source dataset
uspto-grants-2008_12
Patent number
US07470723B2

Reaction notes

Loading…