N-bromobutanimide → Isohexane ethyl acetate

Compound [18] (0.25-6.2 g, 0.2-4.91 mmol) is taken up in dry dichloromethane (3-85 ml) and, at -78° C., dimethylaminosulfur trifluoride (0.08-1.93 g, 0.6-14.73 mmol) and N-bromosuccinimide (0.05-1.23 g, 0.28-6.87 mmol) are added, and the mixture is warmed to room temperature. After washing with saturated sodium bicarbonate solution, the mixture is concentrated and the byproducts of the reaction are removed by silica gel chromatography (stepwise gradient: ethyl acetate/isohexane) giving compound [22] (0.33-6.47 g, 0.72-14.4 mmol, about 80% yield). The reaction product is dissolved in dichloromethane and, at -78° C., o-nitrobenzyl alcohol (0.08-1.88 g, 0.5-12.28 mmol), 4 Å molecular sieves (0.1-7.5 g), silver trifluoromethanesulfonate (0.18-4.42 g, 0.7-17.19 mmol) and hafnocene dichloride (0.27-6.53 g, 0.7-17.19 mmol) are added, and the mixture is allowed to warm to room temperature. Filtration is followed by washing with saturated sodium bicarbonate solution and concentration. The crude product obtained in this way is purified by chromatography on silica gel (dichloromethane/methanol gradient) and dissolved in dry methanol (3-80 ml), and catalytic amounts of sodium methylate (prepared from 0.001-0.09 g of sodium methylate (prepared from 0.001-0.09 g of sodium in 0.2-2.5 ml of methanol) are added. After the reaction is complete, the mixture is neutralized with an acidic ion exchanger (0.2-6.5 g Amberlite IR-120, H+ -form). Evaporation results in compound [23]. FAB-MS: M+H+ =1186. NMR data consistent with Nicolaou et al., J. Am. Chem. Soc. 114:3127 (1992) and C. W. Hummel, Ph.D. Dissertation, University of California, San Diego (1993).

1. washAfter washing with saturated sodium bicarbonate solution
2. concentrationthe mixture is concentrated
3. customthe byproducts of the reaction are removed by silica gel chromatography (stepwise gradient

ORDレコード

ord-35eb95ae8b7745d7af9494440ffc2180

出典データセット

uspto-grants-1995_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05470843