反应详情

To a cooled (-73°), stirred solution of 5.19 g. of benzhydryl 7-(2-thienylacetamido)-3-formyl-2-cephem-4-carboxylate in 60 ml. of tetrahydrofuran under an argon atmosphere was added 10 ml. of a cold (-10°) 3 molar solution of methylmagnesium bromine in ethyl ether. The reaction mixture was stirred with cooling for 4 minutes after which time 10 ml. of 1N.HCl was added. The solution was then allowed to warm to 0° in an ice bath. The reaction mixture was transferred to separatory funnel with the aid of cold ethyl acetate and 1N.HCl. The organic layer was separated and washed with cold 1N.HCl (2X) and brine (2X), and dried over anhydrous sodium sulfate. Evaporation in vacuo to dryness gave a crude product which was chromatographed on silica gel using a toluene-ethyl acetate gradient to give 3.40 g. (63.9 percent) of the title product as a mixture of diastereoisomeric carbinols. Although both isomers have approximately the same rf value, careful fractionation of the column resulted in the isolation of the pure isomers. Isomer I (that which was eluded from the column first) crystallized from methylene chloride/hexane to provide white crystals (m.p. 133.5°-134.5°): ir (CHCl3) 1782 cm-1 (lactam C = O); nmr (CDCl3) δ1.17 (d, 3, J = 6.0 Hz,--CH(OH)CH3), 2.85 (broad s, 1, --OH), 3.79 (s, 2, side chain CH2), 4.27 (m, 1,--CH(OH)CH3), 5.10 (s, 1, C4 --H), 5.13 (d, 1, J = 4.0 Hz, C6 --H), 5.49 (q, 1, J = 4.0 and 8.0 Hz, C7 --H) and 6.31 (s, 1, C2 --H).

1. temperatureTo a cooled (-73°)
2. stirringThe reaction mixture was stirred
3. temperaturewith cooling for 4 minutes after which time 10 ml
4. temperatureto warm to 0° in an ice bath
5. customThe organic layer was separated
6. washwashed with cold 1N
7. dry with materialHCl (2X) and brine (2X), and dried over anhydrous sodium sulfate
8. customEvaporation in vacuo to dryness
9. customgave a crude product which
10. customwas chromatographed on silica gel using a toluene-ethyl acetate gradient
11. customto give 3.40 g