反应详情

(2-Benzyloxycarbonyl-4-methylpentyl)phosphinic acid (1.14 grams, 4.0 mmole), 4-benzylbenzyl bromide (1.31 grams, 5.0 mmole) and N,O-bis(trimethylsilyl) acetamide (2.44 grams, 12 mmole) were combined in dry methylene chloride (40 ml); the mixture was degassed with a stream of dry nitrogen, then stirred at room temperature for 18 hours and refluxed for 24 hours. The cooled solution was quenched with 1N hydrochloric acid (25 ml). The methylene chloride layer was separated and washed with 1N hydrochloric acid (2×25 ml), dried with magnesium sulfate, filtered and concentrated to a turbid oil. This was dissolved in methanol (10 ml)/toluene (40 ml) and treated with excess trimethylsilyldiazomethane (commercial hexane solution). After 30 minutes the excess trimethylsilyldiazo-methane was destroyed with acetic acid. The solution was concentrated to an oil which was chromatographed (75:25--ethyl acetate:hexane) to give 1.18 grams (62%) of 2-[(4-benzylbenzyl)methoxyphosphinoylmethyl]-4-methylpentanoic acid benzyl ester as a colorless oil.

1. customthe mixture was degassed with a stream of dry nitrogen
2. temperaturerefluxed for 24 hours
3. customThe cooled solution was quenched with 1N hydrochloric acid (25 ml)
4. customThe methylene chloride layer was separated
5. washwashed with 1N hydrochloric acid (2×25 ml)
6. dry with materialdried with magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated to a turbid oil
9. dissolutionThis was dissolved in methanol (10 ml)/toluene (40 ml)
10. additiontreated with excess trimethylsilyldiazomethane (commercial hexane solution)
11. customAfter 30 minutes the excess trimethylsilyldiazo-methane was destroyed with acetic acid
12. concentrationThe solution was concentrated to an oil which
13. customwas chromatographed (75:25--ethyl acetate:hexane)