Hydrochloric Acid → 2-(4-(benzyloxy)-7-bromo-5-fluoro-1-methyl-1H-indol-3-yl)acetic acid

To the solution of 33-3 (8 g, 24 mmol) in THF (30 mL) was added oxalyl chloride (15.4 g, 120 mmol) dropwised at 0° C. The mixture was stirred at room temperature overnight. The volatiles were evaporated to get a yellow residue, which was dissolved in 2,2′-oxydiethanol (50 mL). To the resulting solution were added hydrazine hydrate (6 mL) and potassium hydroxide (6.72 g, 120 mmol). The mixture was heated at 190° C. for 2 h before it was cooled to room temperature. Water (100 mL) was added to the mixture and neutralized with hydrochloric acid to pH=5, then extracted with ethyl acetate (2×50 mL). The organic layers were combined, washed with brine (4×50 mL), dried over MgSO4, filtered, and concentrated under vacuum. The resulting residue was purified on silica gel column chromatography eluting with dichloromethane/methanol (10:1) to afford 33-4 (5 g, 58%) as a yellow solid. LRMS: calc 391.0 and found: 392.1 [M+1].

1. customdropwised at 0° C
2. customThe volatiles were evaporated
3. customto get a yellow residue, which
4. temperatureThe mixture was heated at 190° C. for 2 h before it
5. temperaturewas cooled to room temperature
6. extractionextracted with ethyl acetate (2×50 mL)
7. washwashed with brine (4×50 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. customThe resulting residue was purified on silica gel column chromatography
12. washeluting with dichloromethane/methanol (10:1)

ORD record

ord-535fae3c5fd9463eaabcdfbed2eae52b

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08912220B2