Benzyl Alcohol → 3-(Benzyloxy)-5-bromopyridine

Temperature

0 °C

The (2RS,3SR)-3-(5-hydroxypryid-5-yl)-3-methoxy-2-methyltetrahydrofuran used as a starting material was obtained as follows: 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 2-methyltetrahydrofuran-3-one (5 g) 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. There was thus obtained (2RS,3SR)-3-(5-benzyloxypyrid-3-yl)-3-hydroxy-2-methyltetrahydrofuran (7.8 g, 63%), as an oil; the 2-methyl and 3-hydroxy groups being in a cis-relationship.

1. customwas obtained
2. temperatureto warm to ambient temperature
3. temperaturethe mixture was heated to 60° C. for 2 hours
4. temperatureThe mixture was cooled to ambient temperature
5. custompartitioned between ethyl acetate
6. washThe organic layer was washed with a dilute aqueous hydrochloric acid solution and with a saturated aqueous sodium chloride solution
7. dry with materialdried (MgSO4)
8. customevaporated

ORD record

ord-c96ebcb38f2c4d3ebcb9a686b6bc1526

Source dataset

uspto-grants-1995_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05403859