N-bromobutanimide → Ethyl 5-bromo-2-(pyridin-3-yl)thiazole-4-carboxylate

A tetrahydrofuran (15 mL) solution of ethyl 2-(pyridin-3-yl)thiazole-4-carboxylate (1.17 g, 5.0 mmol) was added to −78° C. solution of potassium bis(trimethylsilyl)amide (12 mL, 6 mmol, 0.5 M in toluene) over 2 min. This reaction mixture was allowed to stir for 1.5 h and then was transferred via canula into a −78° C. solution of N-bromosuccinimide (1.35 g, 7.5 mmol) in tetrahydrofuran (5 mL). This mixture was stirred for 5 min and then the reaction vessel was removed from the cooling bath and allowed to warm to room temperature over 3 h. The reaction was quenched by pouring into a mixture of ether and water. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organics were dried over MgSO4, filtered, and the solvent was removed in vacuo. The residue was subjected to silica gel chromatography (0 to 100% ethyl acetate/hexanes) to give the desired product as a white solid (824 mg, 52%): 1H NMR (300 MHz, CDCl3) δ 9.09 (d, J=2.3 Hz, 1H), 8.71 (dd, J=4.9, 1.3 Hz, 1H), 8.25 (dt, J=8.2, 1.7 Hz, 1H), 7.41 (dd, J=7.9, 4.9 Hz, 1H), 4.48 (q, J=7.3 Hz, 2H), 1.46 (t, J=7.3 Hz, 3H); ESIMS m/z 315.0 (M+2).

1. customwas transferred via canula into a −78° C.
2. stirringThis mixture was stirred for 5 min
3. customthe reaction vessel was removed from the cooling bath
4. customThe reaction was quenched
5. additionby pouring into a mixture of ether and water
6. customThe layers were separated
7. extractionthe aqueous layer was extracted twice with ethyl acetate
8. dry with materialThe combined organics were dried over MgSO4
9. filtrationfiltered
10. customthe solvent was removed in vacuo

ORD-Eintrag

ord-922ebd249cd241afb6ffec5284141735

Quelldatensatz

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08853246B2