Propyne → HCID 57800251, compound

HRID 1188425Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4](I)[C:3]=1[C:16]([F:19])([F:18])[F:17].[CH:20]#[C:21][CH3:22]>[Cu](I)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.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4]([C:20]#[C:21][CH3:22])[C:3]=1[C:16]([F:19])([F:18])[F:17]

Participants

Conditions

Temperature: 50 °C

Procedure

A triethylamine (300 mL) solution of N-[4-chloro-2-iodo-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide (Example 60A) (40 g, 98.6 mmol) was treated with 1-propyne (39.5 g, 988 mmol) followed by copper iodide (0.94 g, 4.9 mmol) and PdCl2(PPh3)2 (6.9 g, 9.8 mmol) in a Parr Bomb at −78° C. The reaction vessel was purged with N2, sealed and heated gradually to 50° C. overnight, then cooled to −78° C. The cooled mixture was diluted with Et2O and filtered through celite. The Et2O solution was washed with water once, brine once, and dried (MgSO4). Filtration and concentration in vacuo followed by radial chromatography (SiO2, 0-10% EtOAc-hexanes gradient) afforded the title compound as a yellow solid (20.5 g, 65%): 1H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 8.60 (d, J=9.0 Hz, 1H), 7.38 (d, J=9.0 Hz, 1H), 2.22 (s, 3H), 1.33 (s, 9H); MS (ES) m/z 318 (M+1) and 320 (M+1, isotope).

Workup

customThe reaction vessel was purged with N2
customsealed
temperaturecooled to −78° C
additionThe cooled mixture was diluted with Et2O
filtrationfiltered through celite
washThe Et2O solution was washed with water once
dry with materialbrine once, and dried (MgSO4)
filtrationFiltration and concentration in vacuo

Sources & evidence

ORD record: ord-c6edcb1b0d224381bba4fedbb4221f77
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673948B2

Reaction notes

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