3-Methoxypropyne → 6-(2,6-Diethyl-phenyl)-4-(3-methoxy-prop-1-ynyl)-2-methyl-nicotinic acid ethyl ester

HRID 251623Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:23])[C:5]1[C:10](Br)=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22])[CH3:2].[CH2:24]([O:27][CH3:28])[C:25]#[CH:26]>C(NC(C)C)(C)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I>[CH2:1]([O:3][C:4](=[O:23])[C:5]1[C:10]([C:26]#[C:25][CH2:24][O:27][CH3:28])=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22])[CH3:2]

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of 4-bromo-6-(2,6-diethyl-phenyl)-2-methyl-nicotinic ethyl ester (308 mg, 0.82 mmol), methyl propargyl ether (0.69 mL, 8.2 mmol), Pd(PPh3)4 (95 mg, 0.082 mmol), and copper iodide (8 mg, 0.041 mmol) in diisopropylamine (8 mL) is heated at 105° C. in a sealed tube. After filtration through celite, the filtrate is concentrated in vacuo and the residue purified by flash chromatography to give 6-(2,6-diethyl-phenyl)-4-(3-methoxy-propyn-1-yl)-2-methyl-nicotinic acid ethyl ester as a yellow oil. 1H NMR (CDCl3) 7.36-7.29 (m, 2H), 7.20-7.15 (m, 2H), 4.47 (q, 2H), 4.32 (s, 2H), 3.41 (s, 3H), 2.62 (s, 3H), 2.38-2.27 (m, 4H), 1.41 (t, 3H), 1.06 (t, 6H).

Workup

filtrationAfter filtration through celite
concentrationthe filtrate is concentrated in vacuo
customthe residue purified by flash chromatography

Sources & evidence

ORD record: ord-e8b6344efb5347e184583b4edba59183
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863454B2

Reaction notes

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