乙基 2-氰基-2-(1,4-二氧杂螺[4.5]癸烷-8-亚基)乙酸甲酯

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of CuI (5.67 g, 29.88 mmol) in tetrahydrofuran (70 mL) was added phenyl lithium (1.8M dibutyl ether) (33.2 mL, 59.76 mmol) at −78° C. and the resulting mixture was allowed to stir at −30° C. for 2 h. To the resulting reaction mixture at −78° c. was added the pre-cooled solution of cyano-(1,4-dioxa-spiro[4.5]dec-8-ylidene)-acetic acid ethyl ester (262) in tetrahydrofuran (30 mL) and the resulting mixture was allowed to stir at −30° C. for 1 h. The reaction was monitored by silica TLC (P-anisaldehyde active). The reaction mixture was quenched with saturated NH4Cl-solution and the reaction mixture was diluted with ethyl acetate and the organic layer was separated. The organic part was dried over Na2SO4 and concentrated under reduced pressure, The resulting crude product was purified over silica gel (normal, 100-200 mesh) column chromatography using a gradient eluent 2% to 10% ethyl acetate in hexane to get cyano-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-yl)-acetic acid ethyl ester (263) (3.8 g, 57.91%), as colorless gummy liquid. To the resulting reaction mixture at −78° c to stir at −30° C. for 1 h The reaction mixture was quenched with saturated NH4Cl-solution the reaction mixture was diluted with ethyl acetate the organic layer was separated The organic part was dried over Na2SO4 concentrated under reduced pressure The resulting crude product was purified over silica gel (normal, 100-200 mesh) column chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 1,4-dioxa-spiro[4.5]decan-8-one (261) (5.0 g, 32.01 mmol) and cyano-acetic acid ethyl ester (3.99 g, 35.31 mmol) in toluene (50 mL) were added acetic acid (0.3 mL, 5.09 mmol) and ammonium acetate (123 mg, 1.60 mmol). A Dean Stark trap and reflux condenser were attached to the reaction flask and the mixture was heated to reflux and stirred for 16 h. Thereafter, the reaction mixture was cooled to 0° C. and quenched with saturated aqueous NaHCO3 (100 ml). The aqueous layer was extracted with ethyl acetate (2×200 ml) and the combined organic layer was dried with sodium sulfate, filtered and concentrated under reduced pressure. The crude yellow oil was re-crystallized with 20% ethyl acetate in hexane to afford pure cyano-(1,4-dioxa-spiro[4.5]dec-8-ylidene)-acetic acid ethyl ester (262) (3.2 g, 39.78%) as a light yellow solid. A Dean Stark trap and reflux condenser the mixture was heated to reflux quenched with saturated aqueous NaHCO3 (100 ml) The aqueous layer was extracted with ethyl acetate (2×200 ml) the combined organic layer was dried with sodium sulfate filtered concentrated under reduced pressure The crude yellow oil was re-crystallized with 20% ethyl acetate in hexane