Hydrochloric Acid → (+/-)-6,6-Dimethyl-bicyclo[3.1.0]hexan-2-ol

Temperature

-78 °C

2,2,6,6-Tetramethylpiperidine (9.70 g, 69 mmol) was taken up in MTBE (100 mL) and chilled to −78° C. n-Butyllithium (43 mL, 1.6 M in n-hexane, 69 mmol) was added cautiously and the resulting solution allowed to stir at −78° C. for 30 minutes. The pale yellow solution was added via cannular transfer to a chilled (0° C.) solution of 2-(4-methyl-pent-3-enyl)-oxirane (4.33 g, 34.3 mmol) in MTBE (30 mL) over 30 minutes, allowed to warm slowly to room temperature and stirred under argon for 18 hours. The solution was then added to 1M aqueous hydrochloric acid (50 mL) and extracted into further MTBE (200 mL). Solvent was removed under reduced pressure and the resulting oil purified by column chromatography (0–40% EtOAc/n-hexane, silica). (±)-6,6-Dimethyl-bicyclo[3.1.0]hexan-2-ol was obtained as a yellow oil. 1H NMR (CDCl3): δ 4.15–4.10 (m, 1H), 2.10–2.00 (m, 1H), 1.90–1.80 (m, 1H), 1.80–1.70 (m, 1H), 1.62 (br s, OH), 1.56 (ddd, 1H, J1=12.9, J2=9.5, J3=2.9), 1.48 (br s, 1H), 1.14 (dd, 1H, J1=6.3, J2=1.2), 0.99 (s, 3H), 0.93 (s, 3H).

1. additionwas added cautiously
2. additionThe pale yellow solution was added via cannular transfer to
3. temperatureto warm slowly to room temperature
4. stirringstirred under argon for 18 hours
5. extractionextracted into further MTBE (200 mL)
6. customSolvent was removed under reduced pressure
7. customthe resulting oil purified by column chromatography (0–40% EtOAc/n-hexane, silica)

ORD record

ord-71f66c341f8243f7811dc8a50e516fe0

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07241792B2