反应详情

To 250 ml of methylene chloride was added 44 g (750 mmole) of 1-aminopropane and 107 g (830 mmole) of N,N-diisopropylethylamine. The resulting mechanically stirred mixture was cooled to +5° C. (internal) and a solution of 2-bromo-4'-propoxyacetophenone (Example 585b) (≤750 mmole) in 250 ml of methylene chloride was added over 6 minutes while strictly maintaining the internal temperature between +5° C. and +15° C. as a moderate exotherm occurred. Toward the end of the addition, the internal temperature was allowed to rise to +20° C. After the addition was complete, the mixture was stirred at +20° C. for 9 minutes and then rapidly cooled to -5° C. whereon a total of 120 g (1500 mmole) of 50% aqueous sodium hydroxide dissolved in 500 ml of water and 159 g (750 mmole) of 2,2,2-trichloroethyl chloroformate were added in alternate aliquots, roughly one eighth of the total for each aliquot, to the stirred reaction mixture. The internal temperature was maintained at between -5° C. and +5° C. during the additions. After stirring an additional 15 minutes, the organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo at 20 torr. The lower boiling impurities were then removed by distillation at 0.2 torr with the bath temperature rising to 200° C. and head temperature up to 130° C. The undistilled pot residue was dissolved in 300 ml of diethyl ether and 300 ml of hexane, filtered through silica gel and concentrated in vacuo to yield 123 g of the desired compound, an oil. An analytical sample was isolated by column chromatography on silica gel eluting with diethyl ether and hexanes.

1. temperatureThe resulting mechanically stirred mixture was cooled to +5° C. (internal)
2. temperaturewhile strictly maintaining the internal temperature between +5° C. and +15° C. as a moderate exotherm
3. additionToward the end of the addition
4. customto rise to +20° C
5. additionAfter the addition
6. temperatureThe internal temperature was maintained at between -5° C. and +5° C. during the additions
7. stirringAfter stirring an additional 15 minutes
8. customthe organic layer was separated
9. washwashed with brine
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated in vacuo at 20 torr
12. customThe lower boiling impurities were then removed by distillation at 0.2 torr with the bath temperature
13. customrising to 200° C.
14. customup to 130° C
15. dissolutionThe undistilled pot residue was dissolved in 300 ml of diethyl ether
16. filtration300 ml of hexane, filtered through silica gel
17. concentrationconcentrated in vacuo