Diiodomethane → HCID 66747888, compound

Diiodomethane (9.6 g, 36 mmol) was added at room temperature, with stirring and under nitrogen, to a solution of 1-(4-Isobutyl-6-methylcyclohex-3-enyl)ethanol 4b (3.5 g, 18 mmol) in hexane (50 ml). After cooling to 5° C. triethylaluminium (1M, 36 ml, 36 mmol) was added over 30 min while the temperature was kept below 5°. The reaction was allowed to return to room temperature and stirred for 16 h, then another portion of diiodomethane (9.6 g, 36 mmol) and triethylaluminium (1M, 36 ml, 36 mmol) were added. After a further 15 h yet more diiodomethane (4.8 g, 18 mmol) and triethylaluminium (1M, 18 ml, 18 mmol) were added. After 2 h stirring, the reaction being still incomplete, the reaction mixture was poured slowly, onto a stirred mixture of ice and water. The phases were separated and the aqueous one extracted twice with hexane. The combined organic layers were washed with water, twice with 2M HCl and again with water, dried (Na2SO4) and the solvent removed in vacuo. The crude oil (5.7 g) was dissolved in methylene chloride (50 ml) and solid 3-chloroperbenzoic acid (ca. 77%, 1.5 g, 6.7 mmol) was added in four portions under nitrogen. The mild exothermic effect was controlled with a cool water bath. The reaction was stirred till the unreacted 4b had been completely consumed (30 min). 2M NaOH was added and the mixture stirred until it became white. The phases were separated and the upper aqueous layer extracted twice with methylene chloride. The combined organic layers were washed twice with 2M NaOH and water, dried (MgSO4) and evaporated in vacuo to give 4.6 g of oil. The crude oil was purified by flash chromatography (MTBE/hex. 3:2) and combination of pure fractions gave 5b as a 1:1.1:1.8 mixture of diastereomers (3.4 g, 86% yield, colourless oil, 95% pure). Subsequent distillation provided an olfactory pure sample.

1. additionwas added over 30 min while the temperature
2. customwas kept below 5°
3. customto return to room temperature
4. stirringAfter 2 h stirring
5. customThe phases were separated
6. extractionthe aqueous one extracted twice with hexane
7. washThe combined organic layers were washed with water, twice with 2M HCl and again with water
8. dry with materialdried (Na2SO4)
9. customthe solvent removed in vacuo
10. dissolutionThe crude oil (5.7 g) was dissolved in methylene chloride (50 ml)
11. customThe mild exothermic effect was controlled with a cool water bath
12. customhad been completely consumed (30 min)
13. addition2M NaOH was added
14. stirringthe mixture stirred until it
15. customThe phases were separated
16. extractionthe upper aqueous layer extracted twice with methylene chloride
17. washThe combined organic layers were washed twice with 2M NaOH and water
18. dry with materialdried (MgSO4)
19. customevaporated in vacuo

ORD record

ord-1e1f85c8ce9a43519d62d14f2abf8660

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08999914B2