Preparation of (3R,6R)-2-(hydroxymethylene)-6-isopropyl-3-methylcyclohexane
A solution of (2S,5R)-Menthone (71 g, 0.5 mol) dissolved in THF
(150 cm3) was prepared in a three necked round-bottomed fitted with
dropping funnel and condenser. A suspension of NaH (55.58 g, 1.38 mol) in THF
(150 cm3) was added over 0.25h. A colourless gas was evolved. Ethyl
formate (93.4 cm3, 1.2 mol) was added dropwise over 2h. whilst
stirring with a mechanical stirrer. The mixture was stirred for a further 16 h.
forming a viscous yellow mull. After quenching with isopropylalcohol (10
cm3), water was added (500 cm3). The aqueous layer was
separated and the organic layer extracted with 3 x 100 cm3 water.
The combined aqueous extracts were washed with 3 x 100 cm3 Et2O. The
aqueous layer was then acidified with concentrated HCl to pH1, forming a white
emulsion with a layer of orange oil. The oil was extracted with 3 x 100
cm3 Et2O and dried with MgSO4. Solvent was removed under reduced
pressure to leave an orange oil (75 g, 89% yield). The oil comprised of a 3.5:1
ratio of (3R,6R)- and
(3R,6S)-2-(hydroxymethylene)-6-isopropyl-3-methylcyclohexanones
according to 1H NMR and g.c.:
1H NMR (CDCl3, 270 MHz) d 8.73 (s, 1H), 2.78 (m, 2H), 2.22 (m, 1H),
1,77 (m, 3H), 1.53 (m, 1H), 1.18 (d, J = 6.96 Hz, 3H), 1.00 (d, J
= 6.96 Hz, 3H), 0.79 (d, J = 6.78 Hz, 3H) ppm; G.C. [100
oC (5 min) / inc.temp.10 oC / min / 200 oC (3
min)] RT (relative area) =11.73 [(3R,6R)-, 3.6], 11.82
[(3R,6S)-, 1] min.
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