Methyl vinyl ketone → (3E)-4-[2-(4-isopropoxyphenoxy)-1,3-thiazol-5-yl]but-3-en-2-one

HRID 2078450Notes

Reaction equation

I[C:2]1[S:6][C:5]([O:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)=[N:4][CH:3]=1.C(N(CC)CC)C.[CH3:25][C:26]([CH:28]=[CH2:29])=[O:27]>CN(C)C=O.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.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>[CH:15]([O:14][C:11]1[CH:12]=[CH:13][C:8]([O:7][C:5]2[S:6][C:2](/[CH:29]=[CH:28]/[C:26](=[O:27])[CH3:25])=[CH:3][N:4]=2)=[CH:9][CH:10]=1)([CH3:17])[CH3:16]

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of the product from Example 7B (1.6 g, 4.43 mmole) in N,N-dimethylformamide (25 mL) was consecutively added triethylamine (8 mL), tetrabutyl ammonium chloride (1.2 g, 4.3 mmole), methylvinylketone (2 g, 28.5 mmole) and dichlorobis(triphenylphosphine)palladium(II) (155 mg, 0.22 mmole). The reaction mixture was heated at 75° C. overnight. The reaction mixture was diluted with ethyl acetate and washed with 0.5N aqueous HCl, followed by brine. The reaction mixture was dried over magnesium sulfate filtered and evaporated. The product was purified via silica column, using a gradient of 5-25% ethyl acetate in hexane, to yield 1.15 g (85%) of orange solid. 1H NMR (300 MHz, CDCl3) δ ppm 7.50 (d, J=15.44 Hz, 1H) 7.42 (s, 1H) 7.13-7.24 (m, 2 H) 6.84-7.00 (m, 2H) 6.23 (d, J=15.81 Hz, 1H) 4.38-4.63 (m, 1H) 2.30 (s, 3H) 1.35 (t, J=5.52 Hz, 6H). Mass spectrum DCI 304 (M+H)+.

Workup

washwashed with 0.5N aqueous HCl
dry with materialThe reaction mixture was dried over magnesium sulfate
filtrationfiltered
customevaporated
customThe product was purified via silica column

Sources & evidence

ORD record: ord-6ff95b0b1cc64805a880f211cde9b128
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07928243B2

Reaction notes

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