反应详情

温度

5 °C

The syn isomer of 2-(1-t-butoxycarbonylcyclobutoxyimino)-2-(2-tritylaminothiazol-4-yl)-acetic acid prepared according to Belgian Patent 876,541 (4.42 g) and 4-dimethylaminopyridine (0.25 g) are added to a solution of the E form of 7-amino-2-benzhydryloxycarbonyl-8-oxo-3-(2-tosyloxyvinyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide (product 7d) (4.34 g) in methylene chloride (50 cc). The mixture is cooled to 5° C. and a solution of N,N'-dicyclohexylcarbodiimide (1.69 g) in methylene chloride (30 cc) is added dropwise in the course of 10 minutes. The temperature is left to rise, the mixture is stirred for 4 hours at 20° C. and concentrated to dryness at 20° C. under 20 mm Hg (2.7 kPa) and the residue is taken up in ethyl acetate (200 cc). The solution is washed with water (2×100 cc), 0.1 N hydrochloric acid (100 cc), a saturated aqueous solution of sodium bicarbonate (100 cc) and water (100 cc), dried over sodium sulphate and filtered and the filtrate is concentrated to dryness at 25° C. under 20 mm Hg (2.7 kPa). The residue is chromatographed on a column of Merck silica gel (0.06-0.2) (180 g) (diameter of the column: 3 cm, height: 60 cm). Elution is carried out with a 70/30 (by volume) cyclohexane/ethyl acetate mixture (1 liter), 60 cc fractions being collected. Fractions 6 to 10 are concentrated to dryness at 20° C. under 20 mm Hg (2.7 kPa) and this yields a product (7a) (2.7 g) in the form of a cream-coloured powder.

1. waitThe temperature is left
2. concentrationconcentrated to dryness at 20° C. under 20 mm Hg (2.7 kPa)
3. washThe solution is washed with water (2×100 cc), 0.1 N hydrochloric acid (100 cc)
4. dry with materiala saturated aqueous solution of sodium bicarbonate (100 cc) and water (100 cc), dried over sodium sulphate
5. filtrationfiltered
6. concentrationthe filtrate is concentrated to dryness at 25° C. under 20 mm Hg (2.7 kPa)
7. customThe residue is chromatographed on a column of Merck silica gel (0.06-0.2) (180 g) (diameter of the column
8. washElution
9. custombeing collected
10. concentrationFractions 6 to 10 are concentrated to dryness at 20° C. under 20 mm Hg (2.7 kPa)