3,3-Dimethyl-1-butyne → 2-(3,3-Dimethyl-but-1-ynyl)-6-fluoro-4-nitro-phenylamine

HRID 1403916Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([F:11])[C:3]=1[NH2:12].[CH3:13][C:14]([CH3:18])([CH3:17])[C:15]#[CH:16]>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>[CH3:13][C:14]([CH3:18])([CH3:17])[C:15]#[C:16][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([F:11])[C:3]=1[NH2:12]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-bromo-6-fluoro-4-nitro-phenylamine (11 g, 47 mmol) in dry Et3N (100 mL) was added CuI (445 mg, 5% mol), Pd(PPh3)2Cl2 (550 mg, 5% mol) and 3,3-dimethyl-but-1-yne (9.6 g, 120 mmol) under N2 protection. The mixture was stirred at 80° C. for 10 h. The reaction mixture was filtered, poured into ice (100 g), and extracted with EtOAc (50 mL×3). The combined organic extracts were dried over anhydrous Na2SO4 and evaporated under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 50:1) to give 2-(3,3-dimethyl-but-1-ynyl)-6-fluoro-4-nitro-phenylamine (4.0 g, 36%). 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J=1.2 Hz, 1H), 7.84 (dd, J=2.4, 10.8 Hz, 1H), 4.85 (brs, 2H), 1.36 (s, 9H).

Workup

filtrationThe reaction mixture was filtered
additionpoured into ice (100 g)
extractionextracted with EtOAc (50 mL×3)
dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
customevaporated under vacuum
customto give the crude product, which
customwas purified by column chromatography on silica gel (petroleum ether/ethyl acetate 50:1)

Sources & evidence

ORD record: ord-ea631a323dc7468893a9c8376ee113a6
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912199B2

Reaction notes

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