4,4-Dimethyl-2-pentyne → N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide

HRID 1908423Notes

Reaction equation

Br[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:14])[CH2:11][CH2:12][CH3:13].[CH3:15][C:16]([CH3:21])([CH3:20])[C:17]#[C:18]C>CCN(CC)CC.[Cu]I.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>[CH3:15][C:16]([CH3:21])([CH3:20])[C:17]#[C:18][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:14])[CH2:11][CH2:12][CH3:13]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2H), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H).

Workup

filtrationThe cooled mixture was filtered
extractionthe filtrate was extracted with EtOAc (40 mL×3)
washThe organic layers were washed with sat. NaCl
dry with materialdried over anhydrous Na2SO4
customevaporated under vacuum
customThe crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-ec7bfba378ec47f38b233af7e27e05a2
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598181B2

Reaction notes

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