Dimethylformamide dimethyl acetal → 4-Bromo-6-fluoro-1H-indole

1-Bromo-5-fluoro-2-methyl-3-nitrobenzene (2.00 g, 8.55 mmol) and (dimethoxymethyl)dimethylamine (5.66 mL, 42.7 mmol) in dry DMF (20 mL) was refluxed under N2 for 8 h, then rt. over night. The mixture was diluted with DCM and extracted 5 times with water. The organic layer was dried, filtered and concentrated under reduced pressure. The residue was dissolved in AcOH (10 mL) and added drop wise to a boiling mixture of Fe(s, fine powder) in AcOH (10 mL). The mixture was refluxed for 40 min., partitioned between DCM and saturated aq. Na2CO3/brine (the mixture was filtered through celite before phase separation). The water layer was extracted once more with DCM. The organic layers were combined, dried and concentrated. Purification was performed by flash column chromatography (DCM/hexane 1:3) and afforded the title compound (660 mg, 39%) as a yellow oil. MS (ESI+) for C8H5BrFN m/z 214 (M+H)+.

1. customrt
2. waitover night
3. extractionextracted 5 times with water
4. customThe organic layer was dried
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in AcOH (10 mL)
8. additionadded drop
9. additionwise to a boiling mixture of Fe(s, fine powder) in AcOH (10 mL)
10. temperatureThe mixture was refluxed for 40 min.
11. custompartitioned between DCM and saturated aq. Na2CO3/brine (the mixture
12. filtrationwas filtered through
13. customcelite before phase separation)
14. extractionThe water layer was extracted once more with DCM
15. customdried
16. concentrationconcentrated
17. customPurification

ORD record

ord-f2f2742460d944afa850ee98b3a155e2

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812017B2