Réaction #614624

Équation de réaction

4-oxopentanoic acid

(4-fluorophenyl)hydrazine hydrochloride

sulfuric acid

methanol

→

title compound

Rendement 84.0%

methyl 2-(5-fluoro-2-methyl-1H-indol-3-yl)acetate

Rendement 84.0%

Conditions de réaction

Traitement

1. 1
   ConcentrationThe alcoholic solution was concentrated to about one-third of its original volume
2. 2
   Autretransferred to a phase separator syringe
3. 3
   workup.ADDITIONfilled with cold water (2 mL)
4. 4
   ExtractionThe organic compound was repeatedly extracted with dichloromethane (3×3 mL)
5. 5
   Lavagethe combined organic phases were washed with brine (2 mL)
6. 6
   Séchagedried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   AutreRemoval of the organic solvent and treatment of the residue with a little hexane

Mode opératoire

A stirred mixture of 39.3 mg (0.34 mmol) of 4-oxopentanoic acid,* 50 mg (0.31 mmol) of (4-fluorophenyl)hydrazine hydrochloride, 1 mL of methanol and 40 μL of concentrated sulfuric acid in a 2 mL microwave process vial was heated for 10 min at 120° C. under argon in a microwave synthesizer. The alcoholic solution was concentrated to about one-third of its original volume and then transferred to a phase separator syringe filled with cold water (2 mL). The organic compound was repeatedly extracted with dichloromethane (3×3 mL) and the combined organic phases were washed with brine (2 mL), dried over Na2SO4 and filtered. Removal of the organic solvent and treatment of the residue with a little hexane afford the title compound in 84% yield (39 mg) as viscous mass. C12H12FNO2, Mr=221.23; 1H NMR (400 MHz, DMSO-d6) d: 2.31 (s, 3H), 3.57 (s, 3H), 3.65 (s, 2H), 6.81 (td, J=2.4/9.2 Hz, 1H), 7.10 (dd, J=2.4/10.0 Hz, 1H), 7.21 (dd, J=4.4/8.8 Hz, 1H), 10.97 (s, 1H); 19F NMR (282 MHz, DMSO-d6) d: −123.78 (d, 5′-F); LCMS (ESI) tR: 2.18 min (95%, UV220, ELSD), m/z: 222.2 [M+1]+. [* instead of the acid one could also use the methyl ester with the same outcome]

Source