Methyl iodide → {2-[6-Chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-ethyl}-methyl-carbamic acid tert-butyl ester

To a solution of 14.1 g (36.1 mmol) {2-[6-chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-ethyl}-carbamic acid tert-butyl ester in 360 ml dry tetrahydrofuran were slowly added 44 ml (40 mmol) of a 0.91 M solution of potassium hexamethyldisilazide in tetrahydrofuran at −78° C. After stirring for 20 min. were added 2.5 ml (40 mmol) iodomethane at −78° C. Stirring was continued for 15 min. at −78° C. The cooling bath was removed and the mixture was stirred for another 3 h at room temperature. Quenching with water was followed by evaporation of the solvent in a rotary evaporator. The residue was diluted with a mixture of 200 ml water and 100 ml of a saturated aqueous solution of ammonium chloride. After extraction with three 250-ml portions of tert-butyl methyl ether the combined organic extracts were washed with 200 ml of an ice-cold 0.2 M aqueous solution of hydrochloric acid and 100 ml brine, dried over sodium sulfate and concentrated in vacuo to give 14.9 g of the crude product as a brown oil.

1. customat −78° C
2. stirringStirring
3. waitwas continued for 15 min. at −78° C
4. customThe cooling bath was removed
5. stirringthe mixture was stirred for another 3 h at room temperature
6. customQuenching with water
7. customwas followed by evaporation of the solvent in a rotary evaporator
8. additionThe residue was diluted with a mixture of 200 ml water and 100 ml of a saturated aqueous solution of ammonium chloride
9. extractionAfter extraction with three 250-ml portions of tert-butyl methyl ether the combined organic extracts
10. washwere washed with 200 ml of an ice-cold 0.2 M aqueous solution of hydrochloric acid and 100 ml brine
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated in vacuo

ORD record

ord-67b8d8ff88214b0cbb8dd87504a0d6dd

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143281B2