Dimethylformamide → HCID 58418780, compound

Temperature

-78 °C

To a solution of 90.0 g (0.40 mol) of 4-bromo-1-methoxyindane in 200 ml of anhydrous THF 166 ml (0.42 mol) 2.5 M solution of nBuLi in hexanes was added dropwise by vigorous stirring at −78° C. This solution was stirred at this temperature for 1 hour, cooled to −100° C., and then 57.9 g (0.80 mol) of DMF was added dropwise to maintain temperature of the reaction mixture below −70° C. Further on, this mixture was stirred at room temperature for 3 hours, and then 15 ml of water was added. The resulting mixture was evaporated to dryness. The residue dried in vacuum was dissolved in a mixture of 600 ml of THF and 300 ml of methanol. To this solution 48.2 g (1.27 mol) of NaBH4 was added in small portions by vigorous stirring at 0° C. This mixture was stirred for 12 hours at room temperature and then evaporated to dryness. The formed alcohol was extracted from a mixture of the residue with 800 ml of water by 2×400 ml of dichloromethane. The combined organic extract was dried over Na2SO4 and then evaporated to dryness. The residue was dissolved in 1 liter of THF, and 104 g (0.40 mol) of triphenylphosphine was added. This mixture was stirred for 10 minutes, and then 70.5 g (0.40 mol) of N-bromosuccinimide was added. The resulting mixture was stirred for 30 minutes at room temperature. The product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent: hexanes and then hexanes-ether=10:1, vol.). Yield 74.7 g (78%) of the title material. Anal. calc. for C11H13BrO: C, 54.79; H, 5.43. Found: C, 54.55; H, 5.54. 1H NMR (CDCl3): δ 7.43 (m, 1H, 7-H), 7.31 (m, 1H, 5-H), 7.27 (m, 1H, 6H), 4.88 (dd, J=6.3 Hz, J=4.0 Hz, 1H, CHOMe), 4.52 (m, 2H, CH2Br), 3.47 (s, 3H, OMe), 3.15 (m, 1H, 3-H), 2.93 (m, 1H, 3′-H), 2.42 (m, 1H, 2-H), 2.19 (m, 1H, 2′-H).

1. stirringThis solution was stirred at this temperature for 1 hour
2. temperaturecooled to −100° C.
3. temperatureto maintain temperature of the reaction mixture below −70° C
4. stirringFurther on, this mixture was stirred at room temperature for 3 hours
5. customThe resulting mixture was evaporated to dryness
6. customThe residue dried in vacuum
7. dissolutionwas dissolved in a mixture of 600 ml of THF and 300 ml of methanol
8. stirringby vigorous stirring at 0° C
9. stirringThis mixture was stirred for 12 hours at room temperature
10. customevaporated to dryness
11. extractionThe formed alcohol was extracted from a mixture of the residue with 800 ml of water by 2×400 ml of dichloromethane
12. extractionThe combined organic extract
13. dry with materialwas dried over Na2SO4
14. customevaporated to dryness
15. dissolutionThe residue was dissolved in 1 liter of THF
16. stirringThis mixture was stirred for 10 minutes
17. stirringThe resulting mixture was stirred for 30 minutes at room temperature
18. customThe product was isolated by flash chromatography on silica gel 60 (40-63 μm, eluent

ORD record

ord-c29cb71691d5428c9a9e5b9c5a62d115

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08058461B2