Reacción #219299

Ecuación de reacción

methanesulfonic acid

[4-Fluoro-2-(2-methyl-allyl)-phenyl]-carbamic acid tert-butyl ester

anisole

trifluoroacetic acid

→

2,2-dimethyl-5-fluoroindoline

Rendimiento 66.0%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solvent was removed
2. 2
   Otrothe reaction was transferred to a microwave reaction
3. 3
   TemperaturaThe reaction was cooled to room temperature
4. 4
   Otroquenched
5. 5
   workup.STIRRINGinto excess stirring 1 M NaOH
6. 6
   ExtracciónThe aqueous phase was extracted twice with ethyl acetate
7. 7
   Secadothe combined organics were dried over MgSO4
8. 8
   Filtraciónfiltered
9. 9
   OtroThe resulting oil was purified on silica gel using a gradient of 0-70% t-butyl ethyl ether and hexane

Procedimiento

A sample of [4-Fluoro-2-(2-methyl-allyl)-phenyl]-carbamic acid tert-butyl ester (1.10 g, 4.14 mmol) was treated with anisole (5 mL), dichloromethane (5 mL) and trifluoroacetic acid (5 mL) and stirred for 4 hours. The solvent was removed and the reaction was transferred to a microwave reaction vial using methanesulfonic acid (3 mL). The reaction was heated to 170° C. for 10 minutes. The reaction was cooled to room temperature and quenched into excess stirring 1 M NaOH. The aqueous phase was extracted twice with ethyl acetate and the combined organics were dried over MgSO4 and filtered. The resulting oil was purified on silica gel using a gradient of 0-70% t-butyl ethyl ether and hexane to afford 450 mg (66% yield) of 2,2-dimethyl-5-fluoroindoline; 1H NMR (CDCl3, 400 MHz) δ 1.08 (s, 6H), 2.58 (s, 2H), 6.24 (dd, 1H, J1=4.4, J2=8.4), 6.43-6.48 (m, 1H), 6.53-6.56 (m, 1H); HPLC-MS calcd. for C10H12FN (M+H+) 166.1, found 166.4.

Fuente