One-Pot Process for the Preparation of a -Alkynyl 
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- 作者：Mark L. Boys ; Kimberly J. Cain-Janicki ; Wendel W. Doubleday ; Payman N. Farid ; Mangalya Kar ; Sean T. Nugent ; James R. Behling ; and Daniel R. Pilipauskas
- 刊名：Organic Process Research & Development
- 出版年：1997
- 出版时间：May 1997
- 年：1997
- 卷：1
- 期：3
- 页码：233 - 239
- 全文大小：303K
- 年卷期：v.1,no.3(May 1997)
- ISSN：1520-586X
文摘
The large-scale preparation of the 
le">-alkynyl le">-amino acidester(±)-1,1-dimethylethyl3-amino-5-(trimethylsilyl)-4-pentynoate(A) is discussed. It was discovered that addition of acatalyticamount of lithium bis(trimethylsilyl)amide (LHMDS) toamixture of tert-butyl acetate andN,3-bis(trimethylsilyl)-2-propyn-1-imine (B) initiated a self-perpetuating reactionandgave high yields of the le">-amino ester A upon quench.Thisone-pot procedure eliminated the need to prepare theunstablelithium tert-butyl acetate in a separate reactor and enabledthereaction to be scaled up and run at a more acceptableprocesstemperature (-20 
C) compared to the analogous two-potreaction (-45 C). Addition of 3-(trimethylsilyl)-2-propynaltoLHMDS in THF at -20 C followed bychlorotrimethylsilaneformed the imine B in situ.tert-Butyl acetate (6 equiv) wasadded followed by a substoichiometric quantity(0.15-0.20equiv) of LHMDS. After quenching with aqueousammoniumchloride the product A was obtained in a yield averaging70%.
le">-alkynyl le">-amino acidester(±)-1,1-dimethylethyl3-amino-5-(trimethylsilyl)-4-pentynoate(A) is discussed. It was discovered that addition of acatalyticamount of lithium bis(trimethylsilyl)amide (LHMDS) toamixture of tert-butyl acetate andN,3-bis(trimethylsilyl)-2-propyn-1-imine (B) initiated a self-perpetuating reactionandgave high yields of the le">-amino ester A upon quench.Thisone-pot procedure eliminated the need to prepare theunstablelithium tert-butyl acetate in a separate reactor and enabledthereaction to be scaled up and run at a more acceptableprocesstemperature (-20 C) compared to the analogous two-potreaction (-45 C). Addition of 3-(trimethylsilyl)-2-propynaltoLHMDS in THF at -20 C followed bychlorotrimethylsilaneformed the imine B in situ.tert-Butyl acetate (6 equiv) wasadded followed by a substoichiometric quantity(0.15-0.20equiv) of LHMDS. After quenching with aqueousammoniumchloride the product A was obtained in a yield averaging70%.