216962-18-4

Basic information

• Product Name: 5-(2-phenyl-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester
• Synonyms: 5-(2-phenyl-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester
• CAS NO: 216962-18-4
• Molecular Weight: 373.449
• Mol File: 216962-18-4.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 5-(2-phenyl-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(2-phenyl-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester(216962-18-4)
• EPA Substance Registry System: 5-(2-phenyl-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester(216962-18-4)

Safety Data

• Hazardous Substances Data: 216962-18-4(Hazardous Substances Data)

Upstream product

• 126-30-7 2,2-Dimethyl-1,3-propanediol 
• 15911-11-2 ethyl 4-acetyl-5-methyl-1,2-oxazole-3-carboxylate 
• 216962-12-8 3-isoxazolecarboxylic acid 5-methyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester 
• 100-39-0 benzyl bromide 

Downstream Products

• 691407-01-9 (S)-5-(2-phenyl-1-(t-butyldiphenylsilyloxy)-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester 
• 691407-05-3 5-(2-phenyl-1-(t-butyldiphenylsilyloxy)-ethyl)-4-methoxycarbonylmethyl-3-isoxazolecarboxylic acid ethyl ester 
• 691407-16-6 5-(2-phenyl-1-(t-butyldiphenylsilyloxy)-ethyl)-4-(2-hydroxy-ethyl)-3-isoxazolecarboxylic acid ethyl ester 
• 691407-03-1 5-(2-phenyl-1-(t-butyldiphenylsilyloxy)-ethyl)-4-(1-keto-ethyl)-3-isoxazolecarboxylic acid ethyl ester 
• 691407-07-5 5-(2-phenyl-1-(t-butyldiphenylsilyloxy)-ethyl)-4-(2-oxo-ethyl)-3-isoxazolecarboxylic acid ethyl ester 
• 691406-73-2 (S)-5-(2-phenyl-ethyl)-4-(N-[allyl]-2-amino-2-methoxycarbonyl-ethyl)-3-izoxazolecarboxylic acid ethyl ester 
• 871254-92-1 5-(2-phenyl-1-hydroxy-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester 
• 691406-81-2 (S)-5-(2-phenyl-ethyl)-4-(2-amino-2-methoxycarbonyl-ethyl)-3-isoxazolecarboxylic acid ethyl ester 
• 691406-44-7 5-(2-phenyl-ethyl)-4-(2-hydroxy-ethyl)-3-isoxazolecarboxylic acid ethyl ester 
• 691406-51-6 5-(2-phenyl-ethyl)-4-(2-oxo-ethyl)-3-isoxazolecarboxylic acid ethyl ester 
• 646066-63-9 5-(2-phenyl-1-keto-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl) 3-isoxazolecarboxylic acid ethyl ester 
• 216962-31-1 5-(2-phenyl-ethyl)-4-(methoxycarbonyl)methyl-3-isoxazolecarboxylic acid ethyl ester 
• 646066-62-8 5-(2-phenyl-1-hydroxy-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester 
• 216962-29-7 5-(2-phenyl-ethyl)-4-(1-keto-ethyl)-3-isoxazolecarboxylic acid ethyl ester 

Relevant articles and documents

Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate with 5,5-dimethyl-1,3-dioxanyl as a directing group

Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate, a functionalized isoxazole AMPA analog, occurs cleanly at the C-5 methyl group with 5,5-dimethyl-1,3-dioxanyl as a directing group. The 4-acetyl isoxazole derivatives were transformed selectively by a modified Willgerodt- Kindler reaction into the corresponding homologated methyl esters after deprotection.

An improved procedure for the lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate

Ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate was smoothly lithiated at the 5-methyl position, when the 4-acetyl group was protected with a 5,5-dimethyl-1,3-dioxanyl group. The lithio anion was quenched with a variety of electrophiles such as alkyl halides, aldehydes, TMSCl, and Me3SnCl in good to excellent yields. The lithiation of the unprotected compound and the 4-acetyl group protected as 1,3-dioxolanyl both failed. The effects of different bases have been investigated and the addition of LiCl significantly increased yields. Based on variable temperature NMR studies the 5,5-dimethyl-1,3-dioxanyl group appears to occupy a single chair conformation which may facilitate lateral metalation. This represents a facile entry into 5-functionalized 3-isoxazolyl carboxylic acid derivatives as prodrugs for the AMPA glutamate neurotransmitters of the central nervous system.