2-[1-(phenylsulfanyl)cyclobutyl]acetic acid synthesis

Yield:-

Reaction Conditions:

Stage #1: thiophenolwith potassium carbonate in tetrahydrofuran;water; for 1 h;Heating / reflux;
Stage #2: 2-cyclobutylideneacetic acid in tetrahydrofuran;water;N,N-dimethyl-formamide; for 72 h;

Steps:

81.I

Example 81 : (+/-) l-fS^-dihydro-spiro^H-l-benzothiopyran^.r-cyclobutani^-yD-S-( isoquinolin-5 -yPureaStep I: l-Phenylthiocyclobutane-l -acetic acidA solution of thiophenol (70 mmol) in THF (10 ml) was refluxed for Ih in the presence of of K₂CO₃ (70 mmol) as a base. A solution of Cyclobutylidene acetic acid (intermediate 1) (35 mmol) in DMF (1.0 ml) was added to the above reaction. The reaction was monitored by TLC for completion. After 3 days the reaction was cooled and filtered. It was then neutralized with EPO ethyl acetate saturated with hydrochloric acid and the compound was extracted with ethyl acetate. Organic layer was then separated, dried over anhydrous Na₂SO₄ and concentrated under vacuum. The residue was column purified to give the compound as a yellow solid.

References:

WO2007/42906,2007,A1 Location in patent:Page/Page column 77-78