反应详情

温度

0 °C

To a solution of 5-methoxy-4,4-dimethyl-5-oxopentanoic acid from Step B (7.00 g, 40.2 mmol), in DCM, was added DMF (0.1 mL), followed by the slow addition of oxalyl chloride (5.00 g, 39.4 mmol) over 33 minutes, during which time the reaction flask was maintained under a constant stream of dry nitrogen. Stirring was continued under a light stream of dry nitrogen for an additional hour, during which time the rate of carbon dioxide evolution diminished. This freshly formed acid chloride was then transferred via cannula into a 500 mL round bottom flask, cooled to 0° C., which already contained N-methoxymethanamine hydrochloride (5.76 g, 59.1 mmol) and triethylamine (15.9 g, 158 mmol). Fifteen minutes after complete addition of the acid chloride, the ice bath was removed and the reaction was allowed to warm to ambient temperature. After 1 h at ambient temperature, diethyl ether (100 mL) was added to precipitate some of the triethylamine hydrochloride, which was filtered and washed with more diethyl ether. The combined organics were then washed with 1M HCl (100 mL×2), 1M NaOH (100 mL), water (100 mL), half-saturated brine (100 mL) and saturated brine (100 mL). The organics were then dried over sodium sulfate, filtered and concentrated in vacuo to provide the title compound which was used without further purification. MS: m/z=218 (M+1).

1. temperaturewas maintained under a constant stream of dry nitrogen
2. waitwas continued under a light stream of dry nitrogen for an additional hour, during which time
3. customthe ice bath was removed
4. temperatureto warm to ambient temperature
5. additiondiethyl ether (100 mL) was added
6. customto precipitate some of the triethylamine hydrochloride, which
7. filtrationwas filtered
8. washwashed with more diethyl ether
9. washThe combined organics were then washed with 1M HCl (100 mL×2), 1M NaOH (100 mL), water (100 mL), half-saturated brine (100 mL) and saturated brine (100 mL)
10. dry with materialThe organics were then dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo