Methanol → 2-(5-Methoxy-7-methyl-1H-indol-4-yl)acetonitrile

To a suspension of KOtBu (6.98 g, 62.2 mmol) in THF (50.0 mL) at −78° C. was added TOSMIC (8.10 g, 41.5 mmol) in THF (50.0 mL). The mixture was stirred at −78° for 15 minutes. To the mixture at −78° C. was then added a solution of tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (6 g, 20.74 mmol) in THF (50 mL). The reaction was stirred at −78° C. for 1.5 hours. MeOH (10 ml) was then added and the reaction was removed from the dry ice bath. After 30 minutes the reaction was placed in a 40° C. water bath for 30 minutes. At this point, the reaction was cooled in an ice bath and was quenched with a saturated solution of ammonium chloride and then diluted with water and EtOAc. The layers were separated and the organics layer was dried, concentrated and absorbed onto silica to purify via FCC (0-50% EtOAc:heptanes) to afford the title compound. MS (ESI+) m/z 201.2 (M+H).

1. stirringThe reaction was stirred at −78° C. for 1.5 hours
2. customthe reaction was removed from the dry ice bath
3. waitAfter 30 minutes the reaction was placed in a 40° C.
4. waitwater bath for 30 minutes
5. temperatureAt this point, the reaction was cooled in an ice bath
6. customwas quenched with a saturated solution of ammonium chloride
7. additiondiluted with water and EtOAc
8. customThe layers were separated
9. customthe organics layer was dried
10. concentrationconcentrated
11. customabsorbed onto silica
12. customto purify via FCC (0-50% EtOAc:heptanes)

ORD-Eintrag

ord-e70634ca42c549e2a878e33f7d282f66

Quelldatensatz

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09056874B2