Sulfuric Acid → HCID 90431850, compound

Temperature

-20 °C

Under a nitrogen atmosphere, a diethylzinc solution in toluene (concentration: 15% by weight, 5.4 g, 0.0066 mol) was placed into a 100-ml flask equipped with a stirring apparatus, a dropping funnel, and a thermometer, and cooled to −20° C. Chloroiodomethane (2.33 g, 13.2 mmol) was placed into the dropping funnel, and added dropwise with the temperature kept between −15 and −20° C. After completion of the dropwise addition, the mixture was stirred at −5 to −15° C. for 20 minutes, and then cooled to −25° C. (Z)-2-Methyl-4-(2-methylphenyl)pent-2-en-1-ol (0.62 g, 3.3 mmol) was added dropwise at −20 to −25° C. over a period of 15 minutes. After completion of the dropwise addition, the stirring was continued at −15 to −25° C. for 20 minutes. Next, a 20% aqueous sulfuric acid solution (2.5 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). [(1S*,2S*)-1-Methyl-2-((R*)-1-(2-methylphenyl)ethyl)cyclopropyl]methanol (0.47 g, 2.3 mmol, 70% yield) was obtained as the main isomer, and [(1S*,2S*)-1-methyl-2-((S*)-1-(2-methylphenyl)ethyl)cyclopropyl]methanol (0.12 g, 0.59 mmol, 17% yield) 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 −15 and −20° C
4. additionAfter completion of the dropwise addition
5. additionwas added dropwise at −20 to −25° C. over a period of 15 minutes
6. additionAfter completion of the dropwise addition
7. waitthe stirring was continued at −15 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-f3891053797d40bc817f8e38cb56e183

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296675B2