Molecules 2005, 10
1417
(1S*,2R*,4R*)-3,3-Dimethoxy-1-methyl-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid methyl ester
(5a)
A solution of compound 4a (1.01 g, 4.12 mmol) in methanol (6 mL) was added dropwise to a 1M
solution of sodium methoxide in methanol (20 mL), cooled with an ice bath. The reaction mixture was
stirred for 2 h and then allowed to warm slowly to room temperature. The mixture was cooled again to
4 °C and then treated with 1:1 aqueous hydrochloric acid solution until pH 5. The methanol was
removed under vacuum and the products were extracted with ethyl ether. The combined organic
extracts were washed with saturated brine and dried over anhydrous MgSO4. The solvent was removed
under vacuum and the residue was purified by chromatography in a silica gel column, eluting with
hexane/ethyl acetate (7:3), yielding 0.818 g (87%) of 5a as a yellow solid; m.p. 60-62 °C; 1H-NMR δ:
1.54 (s, 3H), 2.90 (s, 1H), 3.14 (s, 3H), 3.40 (s, 3H), 3.63 (s, 3H), 4.66 (d, 1H, J = 1.8 Hz), 6.36 (dd,
1H, J1 = 5.8 Hz, J2 = 1.8 Hz), 6.61 (d, 1H, J = 5.8 Hz); 13C-NMR δ: 18.2 (CH3), 50.7 (CH3), 51.0
(CH3), 51.7 (CH3), 59.0 (CH), 84.0 (CH), 87.6 (C), 113.0 (C), 131.2 (CH), 140.8 (CH), 169.7 (C=O);
IR (thin film) cm-1: 2953, 2837, 1738; 1436, 1316, 1142, 1060; MS m/z (relative intensity): 146 [M+ -
82] (12%), 115 (31%), 82 (8%), 69 (11%), 59 (9%), 28 (100%), 15 (22%).
(1S*,2R*,4R*)-1-Methyl-3-oxo-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid methyl ester (1)
Conc. hydrochloric acid solution (1.0 mL) was added dropwise at room temperature to a solution
of compound 5a (103.5 mg; 0.454 mmol) in methanol (1.5 mL). The reaction mixture was stirred for 7
h. The resultant mixture was treated with water (1 mL) and extracted with ethyl ether. The organic
extracts were washed with saturated NaHCO3 solution, then dried over anhydrous MgSO4 and the
1
solvent was removed under vacuum, yielding 67.5 mg (82%) of a colorless oil; H-NMR δ: 1.74 (s,
3H), 3.15 (s, 1H), 3.74 (s, 3H), 4.76 (d, 1H, J = 2.0 Hz), 6.40 (dd, 1H, J1 = 5.6 Hz, J2 = 2.0 Hz), 6.75
(d, 1H, J = 5.6 Hz); 13C-NMR δ: 18.4 (CH3), 52.6 (CH3), 55.1 (CH), 83.5 (CH), 87.9 (C), 129.4 (CH),
144.3 (CH), 167.8 (C=O), 199.4 (C=O); IR (thin film) cm-1: 2956, 2840, 1732, 1436, 1303, 1205,
1023.
(1S*,2R*,4R*)-3,3-Dimethoxy-1-methyl-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid methyl ester (6)
A solution of compound 5a (161 mg, 0.707 mmol) in methanol (1 mL) was placed in a 150 mL
stainless steel pressure reactor. After addition of 5% Pd/C (25 mg), the resulting mixture was stirred
under a hydrogen atmosphere at 6 atm and room temperature for 3 h. The reaction mixture was filtered
through silica gel and the residue was washed with ethyl acetate. The organic extracts were dried over
anhydrous MgSO4 and the solvent was removed under vacuum, yielding 126 mg (78%) of a colorless
oil; 1H-NMR δ: 1.40 (ddt, 1H, J1 = J2 = 12.5 Hz, J3 = 5.0 Hz, J4 = 2.0 Hz), 1.48 (s, 3H), 1.77 (ddt, 1H,
J1 = J2 = 12.5 Hz, J3 = 5.8 Hz, J4 = 4.5 Hz), 1.92 (ddd, 1H, J1 = 12.5 Hz, J2 = 9.6 Hz, J3 = 5.0 Hz),
2.80 (d, 1H, J = 2.0 Hz), 2.80 (ddd, 1H, J1 = 12.5 Hz, J2 = 9.6 Hz, J3 = 4.5 Hz), 3.19 (s, 3H), 3.33 (s,
3H), 3.70 (s, 3H), 4.37 (d, 1H, J = 5.8 Hz); 13C-NMR δ: 23.3 (CH3), 24.9 (CH2), 30.0 (CH2), 49.1
(CH3), 51.0 (CH3), 51.6 (CH3), 59.8 (CH), 83.1 (CH), 86.7 (C), 109.7 (C), 169.4 (C=O); IR (thin film)
cm-1: 2951, 2837, 1734, 1213, 1151, 1071.