Sulfuryl chloride → Ethyl 4-chloro-5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

To a solution of ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate (0.7 g, 2.44 mmol) in toluene (30 mL) was added tert-butyl amine (0.014 g, 0.2 mmol) and the mixture was set in an oil bath preheated at 70° C. After 1 min, a solution of sulfuryl chloride (0.37 g, 2.49 mmol) in toluene (1 mL) was added. The reaction was followed by TLC (60% CH2Cl2-hexanes) and additional reagents were added accordingly. After 30 min, more tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.06 g, 0.37 mmol) were added. After another 30 min additional tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.019 g, 0.12 mmol) were added and heating was continued for 30 min. Upon cooling, the mixture was partitioned between EtOAc and 0.2N HCl. The organic phase was washed with 0.2N HCl and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient) to afford the title compound (0.72 g, 92% yield, 95% purity): MS (ES) m/z 322 (M+1).

1. customthe mixture was set in an oil bath
2. custompreheated at 70° C
3. additionwere added accordingly
4. waitAfter 30 min
5. temperatureheating
6. waitwas continued for 30 min
7. temperatureUpon cooling
8. customthe mixture was partitioned between EtOAc and 0.2N HCl
9. washThe organic phase was washed with 0.2N HCl
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient)

ORD-Eintrag

ord-31285f029ba842bca21d6e1fa4f03c41

Quelldatensatz

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08026262B2