Reaction #5446

Reaction equation

diisopropyl ethyl amine

Triethyl orthoformate

product

4-Bromo-7-methoxy-2,3-dihydro-1H-inden-1-one

BF3.Et2O

→

white solid

4-Bromo-7-methoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxaldehyde diethy acetal

Solvents

methylene chloride

methylene chloride

Conditions

Workup

1. 1
   Temperaturecooled to -78° C
2. 2
   TemperatureThe reaction was then warmed to -15° C. for 2 h
3. 3
   Otherquenched in 5% NaHCO3 solution
4. 4
   Extractionextracted with methylene chloride
5. 5
   WashThe organic extracts were washed with brine
6. 6
   Dryingdried (MgSO4)
7. 7
   Otherthe solvent removed
8. 8
   OtherThe crude product was triturated with cold hexane
9. 9
   Otherthe crystalline product collected

Procedure

Triethyl orthoformate (16.5 ml) was cooled to -30° C. and 15.0 ml BF3.Et2O in 50 ml methylene chloride was added. The reaction was warmed to 0° C. for 15 min, and then cooled to -78° C. To the reaction was added 12.05 g of the product from Example 34 in 50 ml methylene chloride, followed by dropwise addition of 19.4 ml diisopropyl ethyl amine. The reaction was then warmed to -15° C. for 2 h, then quenched in 5% NaHCO3 solution and extracted with methylene chloride. The organic extracts were washed with brine, dried (MgSO4), and the solvent removed. The crude product was triturated with cold hexane, and the crystalline product collected to yield 14.60 g of a white solid, mp: 76°-8° C. NMR (CDCl3) δ 1.05 (t, 3H), 1.27 (t, 3H), 3.03 (m, 2 H), 3.30 (m, 1H), 3.43-3.80 (m, 4H), 3.95 (s, 3H), 5.00 (d, 1H), 6.71 (d, 1H), 7.63 (d, 1H).

Source