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US 3,998,875 AGranted
Process of preparing 5-fluoro-2-methyl-1-(paramethylsulfinylbenzylidene)-indenyl-3-acetic acid
AssigneeMerck & Co., Inc.
InventorsRoger J. Tull, David G. Melillg
Life of this patent
Estimating the term…
Abstract
Invention relates to improved processes for preparing 5-fluoro-2-methyl-1-(p-methylsulfinylbenzylidene)-indenyl-3-acetic acid, to intermediates thereof, and to the preparation of said intermediates.
Claims7
A process of preparing 5-fluoro-2-methyl-1para-methylsulfinylbenzylidene)-indenyl-3-acetic acid which comprises the steps of:
- a. acylating fluorobenzene with gamma-carbonylhalide-gamma-valerolactone, gamma-carboxy-gamma-valerolactone or gamma-carboxy-gamma-valerolactone anhydride in the presence of gallium trihalide, aluminum trihalide, antimony trihalide, titanium tetrahalide, boron trihalide or iron trihalide to form gamma-(para-fluorobenzoyl)-gamma-valerolactone;
- or acylating fluorobenzene with gamma-methyl-glutaconic anhydride in the presence of aluminum chloride, polyphosphoric acid, hydrogen fluoride, sulfuric acid, fluoroboric acid, boron trifluoride, boron trichloride or boron tribromide at a temperature of from 0.degree.-85.degree. C to form 4-(para-fluorobenzoyl)-3-pentenoic acid;
- b. cyclizing said gamma-(para-fluorobenzoyl)-gamma-valerolactone or said4-(para-fluorobenzoyl)-3-pentenoic acid at a temperature of from 80.degree.-200.degree. C in an inert solvent in the presence of gallium trihalide, aluminum trihalide, antimony trihalide, titanium tetrahalide, boron trihalide or iron trihalide to form 5-fluoro-2-methyl-indanone-3-acetic acid;
- c. reducing said 5-fluoro-2-methyl-indanone-3-acetic acid in the presence of alkali metal borohydride, aluminum isopropoxide or in the presence of nickel, iridium, rhenium, ruthenium, rhodium, platinum or palladium or a reduced metal oxide thereof and hydrogen under a pressure of from atmospheric to 200 atmospheres in the presence of an inert solvent to form 5-fluoro-2-methyl-indanol-3-acetic acid;
- d. dehydrating said 5-fluoro-2-methyl-indanol-3-acetic acid at a temperature of from 20.degree.-150.degree. C in the presence of an inert solven under acid conditions to form 5-fluoro-2-methyl-ind-1-ene-3-acetic acid or under basic conditions to form 5-fluoro-2-methyl-ind-2-ene-3-acetic acid;
- e. condensing said 5-fluoro-2-methyl-indene acetic acid in the presence of a strong base in an inert solvent with para-methylthiobenzaldehyde followed by oxidation or with para-methyl-sulfinylbenzaldehyde, followed by acidification to produce the desired product.
3 more elements
A process of preparing 5-fluoro-2-methyl-1-(para-methyl-sulfinylbenzylidene)-indenyl-3-acetic acid which comprises the steps of:
- a. acylating fluorobenzene with gamma-carbonylhalide-gamma-valerolactone, gamma-carboxy-gamma-valerolactone or gamma-carboxy-gamma-valerolactone anhydride in the presence of gallium trihalide, aluminum trihalide, antimony trihalide, titanium tetrahalide, boron trihalide or iron trihalide to form gamma-(para-fluorobenzoyl)-gamma-valerolactone;
- b. cyclizing said gamma-(para-fluorobenzoyl)-gamma-valerolactone at a temperature of from 80.degree.-200.degree. C in an inert solvent in the presence of gallium trihalide, aluminum trihalide, antimony trihalide, titanium tetrahalide, boron trihalide or iron trihalide to form 5-fluoro-2-methyl-indanone-3-acetic acid;
- c. reducing said 5-fluoro-2-methyl-indanone-3-acetic acid in the presence of alkali metal borohydride, aluminum isopropoxide or in the presence of nickel, iridium, rhenium, ruthenium, rhodium, platinum or palladium or a reduced metal oxide thereof and hydrogen under a pressure of from atmospheric to 200 atmospheres in the presence of an inert solvent to form 5-fluoro-2-methyl-indanol-3-acetic acid;
- d. dehydrating said 5-fluoro-2-methyl-indanol-3-acetic acid at a temperature of from 20.degree.-150.degree. C in the presence of an inert solvent under acid conditions to form 5-fluoro-2-methyl-ind-1-ene-3-acetic acid or under basic conditions to form 5-fluoro-2-methyl-ind-2-ene-3-acetic acid;
- e. condensing said 5-fluoro-2-methyl-indene-3-acetic acid in the presence of a strong base in an inert solvent with para-methylthiobenzaldehyde followed by oxidation or with para-methyl-sulfinylbenzaldehyde, followed by acidification to produce the desired product.
2 more elements
Dependencies are inferred from the claim text.