Hydrochloric Acid → 3-Cyclohexene-1-carboxylic acid, 6-methyl-, (1R,6R)-rel-

To a cold (0° C.) solution of 7 (103.86 g, 0.286 mol), in 4:1 THF/water (500 mL), was added 30% hydrogen peroxide (160 mL, 1.40 mol), followed by lithium hydroxide (27.4 g, 0.652 mol). The resulting mixture was slowly allowed to warm to room temperature and after 4 h the reaction was complete. The solution was cooled (0° C.) and sodium sulfite (202 g, 1.6 mole) was added. The bulk of the THF was removed in vacuo and the resulting mixture (pH 12-13) was extracted with methylene chloride (5×200 mL) to remove the chiral auxiliary. The combined methylene chloride organics were dried (MgSO4) and the volatiles were removed in vacuo to yield 44.0 g (87% yield) of the recovered benzyloxazolidinone auxiliary. The aqueous layer was acidified to pH 1-2 with 12 M HCl and extracted with ethyl acetate (5×300 mL). The combined ethyl acetate extracts were dried (Na2SO4) and the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6). The methyl ester of 5 was shown to be at 97% ee on a 30 m Chiraldex column. Rf 0.40 (ethyl acetate/hexane 1:1); m.p. 65-66° C.; 1H NMR (300 MHz, CDCl3) δ 10.2-11.8 (b, 1H), 5.61-5.69 (m, 2H). 2.12-2.33 (m, 4H), 1.89-2.00 (m, 1H), 1.67-1.77 (m, 1H), 1.02 (d, J=6.6, 3H); 13C NMR (75 MHz, CDCl3) δ 182.3, 126.3, 124.5, 46.8, 32.9, 30.3, 28.7, 19.7; MS (EI) m/z 140 (M+, 21), 122 ([M-H2O]+, 16), 111 (14), 95 (100), 79 (75), 67 (49); [α]D−99.0° (c=4.89, CHCl3).

1. extractionextracted with ethyl acetate (5×300 mL)
2. dry with materialThe combined ethyl acetate extracts were dried (Na2SO4)
3. customthe volatiles were removed in vacuo
4. customto yield an oil which
5. customwas purified by flash chromatography
6. customto give
7. customa solid (20.2 g, 51% overall yield from 6)

ORD record

ord-3e8ccfc8329645c29ee8ef62dfd7eed2

Source dataset

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06375943B1