Sodium borohydride → 7-bromo-5-fluoro-2-methyl-1H-indene

Temperature

0 °C

To a solution of 48.4 g (199 mmol) of 4-bromo-6-fluoro-2-methylindan-1-one in 270 ml of a mixture of THF-methanol (2:1, vol.), 11.3 g (299 mmol) of NaBH4 was added in small portions, while vigorously stirring, over 2 h at 0° C. This mixture was stirred for 12 h at room temperature and then added to 500 ml of cold water. The organic layer was separated, the aqueous layer was extracted with 3×200 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and then evaporated to dryness. The residue was dissolved in 500 ml of toluene, and 2.0 g of p-TosOH was added. The resulting solution was refluxed for 4 h using a Dean-Stark trap to remove the water formed, and then it was passed through a short Silica Gel 60 column (40-63 um, d 100 mm, l 80 mm, eluent: hexanes). This column was additionally washed with 250 ml of toluene. The combined organic extract was evaporated to dryness. The residue was dried in vacuum to give the title compound. Yield 38.0 g (84%).

1. stirringThis mixture was stirred for 12 h at room temperature
2. customThe organic layer was separated
3. extractionthe aqueous layer was extracted with 3×200 ml of methyl-tert-butyl ether
4. dry with materialThe combined organic fractions were dried over K2CO3
5. customevaporated to dryness
6. dissolutionThe residue was dissolved in 500 ml of toluene
7. addition2.0 g of p-TosOH was added
8. temperatureThe resulting solution was refluxed for 4 h
9. customto remove the water
10. customformed
11. washThis column was additionally washed with 250 ml of toluene
12. extractionThe combined organic extract
13. customwas evaporated to dryness
14. customThe residue was dried in vacuum

ORD record

ord-755c3a04b2a440eeaa606a338d069271

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07446216B2