Tetrahydrofuran → Methyl 4-chloro-3-(2-(4-fluorophenyl)ethynyl)benzoate

HRID 1472500Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1I.[C:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)#[CH:14].O1CCCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:14]#[C:13][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Under an inert atmosphere of nitrogen, a mixture of methyl 4-chloro-3-iodobenzoate (200 mg, 0.68 mmol, 1.00 equiv), 1-ethynyl-4-fluorobenzene (243 mg, 2.02 mmol, 3.00 equiv), Pd(PPh3)2Cl2 (94.6 mg, 0.14 mmol, 0.20 equiv), CuI (13 mg, 0.07 mmol, 0.10 equiv), tetrahydrofuran (12 mL), and triethylamine (4 mL) was stirred overnight at 70° C. in an oil bath. The solids were filtered out, and the filtrate was concentrated in vacuo. The residue was purified via silica gel column chromatography (ethyl acetate/petroleum ether (1:100)) resulting in 130 mg (67%) of methyl 4-chloro-3-(2-(4-fluorophenyl)ethynyl)benzoate as a white solid.

Workup

filtrationThe solids were filtered out
concentrationthe filtrate was concentrated in vacuo
customThe residue was purified via silica gel column chromatography (ethyl acetate/petroleum ether (1:100))
customresulting in 130 mg (67%) of methyl 4-chloro-3-(2-(4-fluorophenyl)ethynyl)benzoate as a white solid

Sources & evidence

ORD record: ord-f908cedb16ff46909627573389de1d69
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012637B2

Reaction notes

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