Ethanol → 4-Chloro-2-(pyridin-3-yl)thiazole

HRID 2199238Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Cl[C:11]1[S:12][CH:13]=[C:14]([Cl:16])[N:15]=1.C(O)C.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:16][C:14]1[N:15]=[C:11]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[S:12][CH:13]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a suspension of pyridin-3-ylboronic acid (3.87 g, 31.5 mmol) in toluene (120 mL) was added 2,4-dichlorothiazole (4.62 g, 30 mmol) followed by ethanol (60 mL) and a 2.0 M solution of K2CO3 (30.0 mL, 60.0 mmol). The solution was degassed by applying vacuum and then purging with nitrogen (3 times). To the reaction mixture was added tetrakis(triphenylphosphine)palladium (0) (1.733 g, 1.500 mmol) and the flask was heated at 95° C. under nitrogen for 16 hours. The aqueous layer was removed and the organic layer was concentrated. The crude product was purified via silica gel chromatography (0-100% ethyl acetate/hexanes) to afford the title compound as a brown solid (4.6 g, 74%): mp 84-86° C.; IR (KBr) 3092 cm−1; 1H NMR (400 MHz, CDCl3) δ 9.16-9.13 (m, 1H), 8.69 (dd, J=4.8, 1.6 Hz, 1H), 8.23 (ddd, J=8.0, 2.2, 1.7 Hz, 1H), 7.40 (ddd, J=8.0, 4.8, 0.8 Hz, 1H), 7.16 (s, 1H).

Workup

customThe solution was degassed
custompurging with nitrogen (3 times)
customThe aqueous layer was removed
concentrationthe organic layer was concentrated
customThe crude product was purified via silica gel chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-9fab6749d3034666be888a0edce2777f
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09357780B2

Reaction notes

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