Trifluoroacetic anhydride → Methyl 8-benzyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate

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Reaction Steps

In an ice bath, NaBH4 (412 mg, 10.6 mmol) was added to a methanol (55 ml) solution of the methyl 8-benzyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate (1.45 g, 5.32 mmol) obtained in Example 17, and the mixture was stirred for 14.5 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added to the reaction mixture and the excess solvent was evapolated under reduced pressure. The residue was adjusted to pH 8.0-8.5 with a saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform. The extract was dried over Na2SO4, filtered and then concentrated in vacuo, and the resulting residue was dissolved in chloroform (30 ml) under a nitrogen atmosphere. To the resulting solution were added triethylamine (1.48 ml, 10.6 mmol) and DMAP as a catalyst, and trifluoroacetic anhydride (1.13 ml, 7.98 mmol) was added thereto in an ice bath, and then the resulting mixture was stirred at room temperature for 21 hours. After completion of the reaction, the reaction mixture was adjusted to pH 9.0 with a saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform. The extract was dried over Na2SO4, filtered and then concentrated in vacuo, and the thus obtained crude product was purified by a silica gel column chromatography (AcOEt:hexane=1:8) to obtain 577 mg of the title compound methyl 8-benzyl-8-azabicyclo[3.2.1]octan-2-ene-2-carboxylate. The yield from the above two steps was 42 mol %. The compound obtained in the present example was a d1-form and was used as a reference standard compound for optical purity measurement.

Provenance & Evidence