Diethyl ether,
Diazomethane,
Alpha-keto ester.

Dimethyl (2RS)-2-(N-(methyloxycarbonyl)amino)-6-oxopimelate (300mg, 1.04mmol) was treated with a solution of CH₂N₂ in diethyl ether at 0^oC for 1h. Solvent was removed in vacuo and the residue purified by flash chromatography (50% EtOAc in hexane, Rf 0.5; 10% CH₃CN in CH₂Cl₂ was also effective, Rf 0.27) to give Dimethyl (2RS, 6RS)-2-(N-(methyloxycarbonyl)amino)-6-epoxymethanopimelate as a colourless oil (273.4mg, 91%).

The key points are: 1. keep the reaction cooled at 0^oC - warming gives methylene insertion compounds. 2. The ethereal solution of diazomethane is made according to the procedure of Vogel (B. S. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatchell, "Vogels Textbook of Organic Chemistry" 5th Ed. Longman, New York, 1989, pp 430-433.) 3. Diazomethane is reputedely toxic, carcinogenic and explosive - the ethereal solution is very much safer than neat diazomethane, but care must be taken to avoid ground glass joints and sharp edges of broken glass to avoid the explosion risk. Use of a blast shield is advised. 4. Small quantities of excess diazomethane/ether ( ca 10ml) are harmlessly destroyed by rotavapping off - for larger quantities neutralise by addidition of glacial acetic acid in ether.

v_max (thin film)/cm^-1 3605, 3510, 3369, 2999, 2955, 1736, 1530, 1440; ¹H(300MHz, CDCl₃, two diastereomers) 5.45 (1H, d, 3J 7.9, NH), 4.35 (1H, m, CH), 3.76, 3.75, 3.74, 3.72, 3.71, 3.68 (9H, 3 x OMe), 3.05 (1H, m, CH), 2.80 (1H, m, CH), 2.17 (1H, m, CH), 1.88 (1H, m, CH), 1.70 (2H, m, CH + CH), 1.55 (2H, m, CH + CH); ¹³C(75.5MHz, CDCl₃, two diastereomers) 172.9, 171.8, 170.6, 170.0, 156.7, 156.6, 58.0, 57.9, 56.63, 56.60, 53.7, 53.4, 52.6, 52.4, 52.3, 52.1, 46.1, 45.6, 32.3, 30.8, 30.62, 29.4, 21.4, 20.8; m/z (CI, CH₄) 290 (MH)⁺, 5%; 258 (M-MeO)⁺, 10%; Calcd. for C₁₂H₂₀NO₇ (MH)⁺ 290.12398, Found 290.12367.

See R. J. Cox, J. A. Durston and D. A. Roper, J. Chem. Soc. Perkin Trans 1., 2002, in press.

Vogel : B. S. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatchell, "Vogels Textbook of Organic Chemistry" 5th Ed. Longman, New York, 1989, pp 430-433.