Ethyl Bromide → (2S,4R)-4-(5-bromothien-2-yl)-4-hydroxy-2-methyltetrahydropyran

Temperature

40 °C

A solution of a mixture of 2,5-dibromothiophene (1.9 g) and ethyl bromide (2.56 g) in THF (6 ml) was added dropwise to a stirred suspension of magnesium (0.29 g) in diethyl ether (3 ml) and the mixture was warmed gently to promote the formation of a Grignard Reagent. The mixture was heated to 40° C. for 1 hour. The mixture was cooled in an ice-bath and a solution of (2S)-2-methyltetrahydropyran-4-one [European Patent Application No. 0385662 (Example 20 thereof); 0.61 g] in THF (5 ml) was added dropwise. The mixture was allowed to warm to ambient temperature and was stirred for 16 hours. The mixture was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was washed with water and with brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography using initially methylene chloride and then increasingly polar mixtures of methylene chloride and diethyl ether as eluent. There was thus obtained, as a less polar isomer, (2S,4R)-4-(5-bromothien-2-yl)-4-hydroxy-2-methyltetrahydropyran (0.248 g, 19%) as an oil, having the 2-methyl and 4-hydroxy groups in a trans-relationship.

1. temperaturethe mixture was warmed gently
2. temperatureThe mixture was cooled in an ice-bath
3. temperatureto warm to ambient temperature
4. extractionextracted with ethyl acetate
5. washThe organic phase was washed with water and with brine
6. dry with materialdried (MgSO4)
7. customevaporated
8. customThe residue was purified by column chromatography
9. temperatureincreasingly polar mixtures of methylene chloride and diethyl ether as eluent

ORD record

ord-c686fc5b6b4249dcb66565adfe96794c

Source dataset

uspto-grants-1996_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05484805