52237-19-1

Synthetic route

trans-4-aminocrotonic acid (38090-53-8) + 4-fluorobenzenediazonium tetrafluoroborate (459-45-0) → β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1)

Conditions	Yield
With hydrogenchloride; titanium(III) chloride In water at 40℃; for 0.583333h; Meerwein arylation;	50%

β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1) + butan-1-ol (71-36-3) → β-(p-fluorophenyl)-γ-aminobutyric acid butyl ester hydrochloride

Conditions	Yield
With hydrogenchloride at 105℃; for 0.5h;	89%

β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1) → 4-{2-[2-(4-Chloro-phenyl)-benzooxazol-5-yl]-propionylamino}-3-(4-fluoro-phenyl)-butyric acid butyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / 3 N HCl / 0.5 h / 105 °C 2: 75 percent / anhydrous sodium hydrogen carbonate / CH2Cl2 / 5 h / Ambient temperature View Scheme

1-({[(2-fluorophenyl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate (1622940-09-3) + β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1) → 4-{[(α-isobutanoyloxyethoxy)carbonyl]amino}-3(R)-(4-fluorophenyl)butanoic acid (1622940-12-8)

Conditions	Yield
With triethylamine In n-heptane; water; acetonitrile at 10 - 20℃;

1-({[(3-fluorophenyl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate (1622939-35-8) + β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1) → 4-{[(α-isobutanoyloxyethoxy)carbonyl]amino}-3(R)-(4-fluorophenyl)butanoic acid (1622940-12-8)

Conditions	Yield
With triethylamine In tert-butyl methyl ether; water; acetonitrile at 10 - 20℃; for 5h;

1-({[(4-trifluoromethylphenyl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate (1622940-11-7) + β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1) → 4-{[(α-isobutanoyloxyethoxy)carbonyl]amino}-3(R)-(4-fluorophenyl)butanoic acid (1622940-12-8)

Conditions	Yield
With triethylamine In tert-butyl methyl ether; water; acetonitrile at 10 - 20℃; for 5h;

1-({[(4-methoxycarbonylphenyl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate (1622939-42-7) + β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1) → 4-{[(α-isobutanoyloxyethoxy)carbonyl]amino}-3(R)-(4-fluorophenyl)butanoic acid (1622940-12-8)

Conditions	Yield
With triethylamine In tert-butyl methyl ether; water; acetonitrile at 10 - 20℃; for 5h;

1-({[(3,4-methylenedioxyphenyl)oxy]carbonyl}oxy)ethyl 2-methylpropanoate (1622939-45-0) + β-(p-fluorophenyl)-γ-aminobutyric acid (52237-19-1) → 4-{[(α-isobutanoyloxyethoxy)carbonyl]amino}-3(R)-(4-fluorophenyl)butanoic acid (1622940-12-8)

Conditions	Yield
With triethylamine In tert-butyl methyl ether; water; acetonitrile at 10 - 20℃; for 5h;

Upstream product

• 38090-53-8 trans-4-aminocrotonic acid 
• 459-45-0 4-fluorobenzenediazonium tetrafluoroborate 

Relevant academic research and scientific papers

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