反应详情

A suspension of sodium hydride (60%, 135 mg, 3.4 mmol) and 1-(6-methyl-3-pyridazinyl)-4-(2-hydroxyethyl)-piperidine (250 mg, 1.1 mmol) in dimethoxyethane (DME; 4 ml) was stirred at room temperature for 2 hr. A solution of 2-chloro-4-t-butyldimethylsilyloxymethylthiazole (385 mg, 1.46 mmol) in DME (1 ml) was added and the mixture stirred at reflux under argon for 5 hr then at room temperature overnight. The mixture was diluted with ether, filtered and then concentrated. The residue was chromatographed on silica gel (25 g; eluent 30%-50% ethyl acetate/hexane) to give 2-1 -(6-methyl-3-pyridazinyl)-4-piperidinylethyl-1-oxy)-4t-butyldimethylsilyloxymethylthiazole (274 mg, 54%), 1H nmr, 0.11 (s, 6H), 0.94 (s, 9H), 1.3-1.87 (m, 7H), 2.58 (s, 3H), 2.93 (t, 2H), 4.31-4.35 (m, 2H), 4.48 (t, 2H), 4,64 (s, 2H), 6.51 (s, 1H), 6.93 (d, 1H), 7.11 (d, 1H).

1. stirringthe mixture stirred
2. temperatureat reflux under argon for 5 hr
3. customat room temperature
4. customovernight
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was chromatographed on silica gel (25 g; eluent 30%-50% ethyl acetate/hexane)