Ammonia → (S)-3-(2-Bromoethyl)-2,3-dihydro-1H-indole-1-carboxylic acid amide

Temperature

3 °C

To a solution of (S)-2-(2,3-dihydro-1H-indol-3-yl)ethanol (23.4 g, 0.14 mol), 37% HCl (aq) (15 mL) and water (15 mL) was added a solution of potassium cyanate (12.6 g, 0.15 mol) in water (85 mL) over a period of 10 min. The resulting mixture was added water (60 mL) and then poured onto a mixture of ice and brine. The aqueous phase was made alkaline by the use of 25% NH3 (aq) and subsequently extracted with ethyl acetate. The combined organic phase was washed with brine and dried (MgSO4). The organic phase was filtered and concentrated in vacuo (19.9 g). The residue was dissolved in tetrahydrofuran (400 mL) and triethylamine (20 mL), which subsequently was cooled to 3° C. To this mixture was added a solution of methanesulfonyl chloride (8.6 mL, 0.11 mol) in tetrahydrofuran (100 mL). The mixture was stirred at room temperature for 30 min, filtered and concentrated in vacuo. The crude product was dissolved in acetone (1400 mL) and lithium bromide (83.8 g, 0.96 mol) was added. The resulting mixture was boiled under reflux for 1 h, filtered and concentrated in vacuo. The residue was purified by flash chromatography (ethyl acetate) and precipitated from ethyl acetate and heptane to give the title compound (8.8 g).

1. extractionsubsequently extracted with ethyl acetate
2. washThe combined organic phase was washed with brine
3. dry with materialdried (MgSO4)
4. filtrationThe organic phase was filtered
5. concentrationconcentrated in vacuo (19.9 g)
6. dissolutionThe residue was dissolved in tetrahydrofuran (400 mL)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. dissolutionThe crude product was dissolved in acetone (1400 mL)
10. temperatureunder reflux for 1 h
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by flash chromatography (ethyl acetate)
14. customprecipitated from ethyl acetate and heptane

ORD record

ord-657f340fad2943989ef628e6c15e9f00

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07544685B2