Efficient synthesis of cyclopropylacetylene

• US 6,072,094 A
• Filed: 07/28/1998
• Issued: 06/06/2000
• Est. Priority Date: 08/06/1997
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Karady, Sandor, Marcune, Benjamin
• Primary Examiner(s): Griffin, Walter D.
• Assistant Examiner(s): Nguyen, Tam M.
• Application Number:
  US09/128,637
• Time in Patent Office: 679 Days
• Field of Search: 585/20, 585/359, 585/534, 585/538
• US Class Current: 585/538
• CPC Class Codes: C07C 13/04 with a three-membered ring
• CPC Class Codes: C07C 2601/02 with a three-membered ring

Abstract

An efficient and facile process for the preparation of cyclopropylacetylene from thioanisole and cyclopropyl substituted ketones or aldehydes is disclosed.

Claims

1. A process for the preparation of cyclopropyl acetylene (CPA), represented by formula I:

##STR13## which comprises reacting a compound represented by formula II;

##STR14## wherein X is H, halo, CF₃, or C_1-6 alkyl;

in the presence of a base and a silylating agent, to a compound represented by formula III;

##STR15## wherein each R is independently a C_1-6 alkyl and X is described above;

reacting a compound of formula III with a compound of formula IV;

##STR16## in the presence of a base to yield a vinyl thioether, represented by formula V and VI;

##STR17## reacting a compound of formula V and VI in the presence of potassium diaminopropane (KAPA) to yield cyclopropyl acetylene.

2. The process of claim 1 wherein the base employed is phenyl lithium, Butyl lithium (BuLi) or potassium methyl and the compound of formula II is reacted with the base at a temperature of about -100°

C. to about -60°

C.

3. The process according to claim 2 wherein the temperature is about -95°

C. to about -70°

C. and the base is BuLi.

4. The process of claim 1 wherein the silylating agent employed are trialkylsilylchlorides, triakylsilyliodides and triflates.

5. The process of claim 4 wherein the silylating agents are trimethylsilylchloride, triethylsilylchloride, t-butyldimethylsilyl chloride, t-butyldiphenylsilylchloride, trimethylsilyltriflate, t-butyldimethylsilyltriflate, triethylsilyltriflate, and triethylsilyliodide.

6. The process of claim 5 wherein the silylating agent is trimethylsilylchloride.

7. A process for the preparation of cyclopropyl acetylene (CPA), represented by formula I:

##STR18## which comprises reacting a compound of formula II;

##STR19## wherein X is H, halo, CF₃, or C_1-6 alkyl;

in the presence of BuLi and TMSCl, to a compound represented by formula III;

##STR20## wherein each R is independently a C₁ alkyl and X is described above;

reacting a compound of formula III with a cyclopropyl carboxaldehyde, represented by formula IV;

##STR21## in the presence of BuLi to yield vinyl thioethers, represented by formula V and VI;

##STR22## reacting a compound of formula V and VI in the presence of potassium diaminopropane (KAPA) to yield cyclopropyl acetylene.