Reaction #216616

Reaction equation

8-fluoro-4-methoxy-2,5-dimethylthiochroman-6-carboxylic acid-1,1-dioxide

1-ethyl-5-hydroxypyrazole

DCC

tert-amyl alcohol

potassium carbonate

→

8-fluoro-4-methoxy-2,5-dimethyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide

Yield 76.8%

Conditions

Workup

1. 1
   Otherto react at 80° C. for 8 hours
2. 2
   workup.DISTILLATIONthe reaction solvent was distilled off under reduced pressure
3. 3
   workup.ADDITIONThe remainder was dispersed in a 2% potassium carbonate aqueous solution and ethyl acetate
4. 4
   Otherto separate it into two phases
5. 5
   Extractionthe precipitated oil was extracted with ethyl acetate
6. 6
   DryingThe extract was dried over anhydrous sodium sulfate
7. 7
   Concentrationconcentrated under reduced pressure

Procedure

In a 50-ml flask, 0.70 g (0.0023 mol) of 8-fluoro-4-methoxy-2,5-dimethylthiochroman-6-carboxylic acid-1,1-dioxide, 0.28 g (0.0025 mol) of 1-ethyl-5-hydroxypyrazole and 0.52 g (0. 0025 mol) of DCC (N,N'-dicyclohexylcarbodiimide) were added to 5 ml of tert-amyl alcohol at the same time, and the mixture was stirred at room temperature for 30 minutes. Then, 0.17 g (0.00125 mol) of anhydrous potassium carbonate was added. The reaction mixture was allowed to react at 80° C. for 8 hours, and then the reaction solvent was distilled off under reduced pressure. The remainder was dispersed in a 2% potassium carbonate aqueous solution and ethyl acetate to separate it into two phases. Further, the aqueous phase was acidified with 5% hydrochloric acid, and the precipitated oil was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give 0.70 g of 8-fluoro-4-methoxy-2,5-dimethyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 40) shown in Table 5. The yield thereof was 78%.

Source