Reaction #2507838

Reaction equation

NaOH

ethyl 4[[4-(4-ethylphenyl)-2,2-dimethyl-[2H]-thiochromen-6-yl]-ethynyl]benzoate

HCl

→

AGN194310

Solvents

THF

ethanol

Conditions

Workup

1. 1
   Temperaturecooled to room temperature
2. 2
   OtherAt the beginning of the process, the reaction mixture formed a heterogeneous system
3. 3
   ExtractionThe mixture was extracted with ethyl acetate (25 ml×2)
4. 4
   WashThe combined organic layers were washed with 10 ml water, saturated aqueous NaCl
5. 5
   Dryingdried with NaSO4
6. 6
   Otherthe solvent was removed under reduced pressure
7. 7
   OtherThe residual solid (0.31 gram) was recrystallized from acetonitrile (25 ml)

Procedure

Two ml of a 2 M solution of NaOH were added to a solution of ethyl 4[[4-(4-ethylphenyl)-2,2-dimethyl-[2H]-thiochromen-6-yl]-ethynyl]benzoate in THF and ethanol. The solution was heated to 40° C., stirred overnight, then cooled to room temperature. The reaction mixture was acidified with 1 N HCl (4 ml). At the beginning of the process, the reaction mixture formed a heterogeneous system. The mixture was extracted with ethyl acetate (25 ml×2). The combined organic layers were washed with 10 ml water, saturated aqueous NaCl, and dried with NaSO4, and the solvent was removed under reduced pressure. The residual solid (0.31 gram) was recrystallized from acetonitrile (25 ml) to yield 4-[[4-(4-ethylphenyl)-2,2-dimethyl-(2H)-thiochroman-6-yl]-ethynyl]benzoic acid, (AGN194310) (0.236 gram, 70%) as a colorless solid (m.p. 210-212° C.) [1H-NMR (DMSO-d6): d8.2 (s, 2H), d7.8 (s, 2H), d7.6 (s, 2H), d7.4 (s, 2H), d7.2 (s, 2H), d7.0 (s, 1H), d6.0 (s, 1H), d2.6 (t, 2H, J=35 Hz), d1.6 (s, 6H), d1.4 (t, 3H, J=46 Hz)].

Source