반응 #741736

반응 방정식

Sodium hydride

benzyl alcohol

3,5-Dibromopyridine

→

5-benzyloxy-3-bromopyridine

수율 67.0%

용매

dimethylformamide

반응 조건

후처리

1. 1
   온도to warm to ambient temperature
2. 2
   온도the mixture was heated to 60° C. for 2 hours
3. 3
   온도The mixture was cooled to ambient temperature
4. 4
   기타partitioned between ethyl acetate
5. 5
   세척The organic layer was washed with a dilute aqueous hydrochloric acid solution and with a saturated aqueous sodium chloride solution
6. 6
   건조dried (MgSO4)
7. 7
   기타evaporated

실험 절차

Sodium hydride (50% w/w dispersion in mineral oil, 5 g) was added portionwise to a mixture of benzyl alcohol (12.4 g) and dimethylformamide (150 ml) which had been cooled to 0° C. The mixture was allowed to warm to ambient temperature and was stirred for 1 hour. 3,5-Dibromopyridine (25.2 g) was added and the mixture was heated to 60° C. for 2 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and a dilute aqueous potassium carbonate solution. The organic layer was washed with a dilute aqueous hydrochloric acid solution and with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was a red oil which on trituration under petroleum ether (b.p. 60°-80° C.) gave 5-benzyloxy-3-bromopyridine (18.6 g, 67%), m.p. 65°-67° C. A solution of a portion (11.5 g) of this product in diethyl ether (500 ml) was cooled to -50° C. and n-butyl-lithium (1.5M in hexane, 32 ml) was added dropwise. The mixture was stirred at -50° C. for 20 minutes, further cooled to -60° C. and a solution of ethyl methoxymethyl ketone (5 g; J. Amer. Chem. Soc., 1946, 68, 2339) in diethyl ether (50 ml) was added. The mixture was stirred at -60° C. for 1 hour and at -30° C. for 30 minutes. A saturated aqueous ammonium chloride solution (200 ml) was added and the mixture was extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 7:3 v/v mixture of toluene and ethyl acetate as eluent. The oil so obtained was triturated under a mixture of petroleum ether (b.p. 60°-80° C.) and diethyl ether. There was thus obtained 2-(5-benzyloxypyrid-3-yl)-1-methoxybutan-2 -ol (5.84 g, 47%), m.p. 83°-84° C.

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