Reaction #597933

Reaction equation

4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

triethylamine

4,4-dimethylcyclohexanamine hydrochloride

N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride

→

title compound

Yield 47.2%

ethyl 6-chloro-7-(4-(4,4-dimethylcyclohexylcarbamoyl)phenoxy)chroman-4-carboxylate

Yield 47.2%

Solvents

EtOAc

DMF

Conditions

Workup

1. 1
   Washwashed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride
2. 2
   DryingThe organic layer was dried over anhydrous sodium sulfate
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated
5. 5
   OtherThe crude material was purified on a Biotage SP1 system
6. 6
   Washeluting with a linear gradient of 5-70% EtOAc in hexanes

Procedure

To a solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (0.0921 g, 0.244 mmol), N,N-dimethylpyridin-4-amine (0.00299 g, 0.0244 mmol), triethylamine (0.0511 ml, 0.367 mmol), and 4,4-dimethylcyclohexanamine hydrochloride (0.060 g, 0.367 mmol) in DMF (1.5 ml) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.0562 g, 0.293 mmol), and the reaction was stirred for 16 hours. The reaction was diluted with EtOAc and washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified on a Biotage SP1 system eluting with a linear gradient of 5-70% EtOAc in hexanes to yield 56 mg of the title compound (47.2% yield).

Source