Sulfuric Acid → HCID 90431843, compound

Temperature

-25 °C

Under a nitrogen atmosphere, a diethylzinc solution in toluene (concentration: 15% by weight, 6.92 g, 8.4 mmol) was placed into a 100-ml flask equipped with a stirring apparatus, a dropping funnel, and a thermometer, and cooled to −25° C. Chloroiodomethane (2.96 g, 16.8 mmol) was placed into the dropping funnel, and added dropwise with the temperature kept between −20 and −25° C. After completion of the dropwise addition, the mixture was stirred at −10 to −20° C. for 15 minutes, and then cooled to −25° C. At the same temperature, (E)-2-methyl-4-(3-methylphenyl)pent-2-en-1-ol (0.80 g, 4.2 mmol) was added dropwise over a period of 20 minutes. After completion of the dropwise addition, the stirring was continued at −10 to −25° C. for 20 minutes. Next, a 20% aqueous sulfuric acid solution (3.1 ml) was added. After stirring for 10 minutes, the aqueous layer was separated, and the organic layer was washed twice with water (10 ml). The solvent was recovered under reduced pressure to obtain a condensed residue. This residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1). [(1R*,2S*)-1-Methyl-2-((R*)-1-(3-methylphenyl)ethyl)cyclopropyl]methanol (0.38 g, 1.9 mmol, 45% yield) was obtained as the main isomer, and [(1R*,2S*)-1-methyl-2-((S*)-1-(3-methylphenyl)ethyl)cyclopropyl]methanol (0.014 g, 0.069 mmol, yield 1.6%) was obtained as a minor isomer. The relative configurations of the main isomer and the minor isomer were determined by NOESY measurement.

1. customequipped with a stirring apparatus, a dropping funnel
2. additionadded dropwise with the temperature
3. customkept between −20 and −25° C
4. additionAfter completion of the dropwise addition
5. temperaturecooled to −25° C
6. additionAfter completion of the dropwise addition
7. waitthe stirring was continued at −10 to −25° C. for 20 minutes
8. stirringAfter stirring for 10 minutes
9. customthe aqueous layer was separated
10. washthe organic layer was washed twice with water (10 ml)
11. customThe solvent was recovered under reduced pressure
12. customto obtain a condensed residue
13. customThis residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1)

ORD record

ord-b258314603c744ff84921a04e9b51182

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296675B2