Methyl iodide → 4-Bromo-2-methyl-1-(methyloxy)-2,3-dihydro-1H-indene

Temperatur

5 °C

To a solution of 149.5 g (0.664 mol) of 4-bromo-2-methyl-1-indanone in 900 ml of THF-methanol (2:1, vol.), 37.6 g (0.995 mol) of NaBH4 was added in small portions at vigorous stirring for 1.5 hours at 5° C. This mixture was stirred at room temperature for 12 hours and then added to 2 L of cold water. The hydrogenation product was extracted with 5×200 ml of dichloromethane, and the combined extract was evaporated to dryness. To 149 g (2.65 mol) of KOH in 420 ml of DMSO, 188 g (82.5 ml, 1.33 mol) of MeI, and a solution of crude 4-bromo-2-methylindan-1-ol in 220 ml of DMSO were added. This mixture was stirred for 2 hours at ambient temperature; then, 92.0 g (40.4 ml, 0.664 mol) of MeI was added, and the mixture was additionally stirred for 2 hours. The resulting mixture was added to 2.5 L of cold water. The crude product was extracted with 5×200 ml of dichloromethane. The combined extract was dried over Na2SO4 and, then, evaporated to dryness. Fractional distillation gave a mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg. Yield, 148.5 g (93%) of a colorless oil.

1. stirringThis mixture was stirred at room temperature for 12 hours
2. extractionThe hydrogenation product was extracted with 5×200 ml of dichloromethane
3. extractionthe combined extract
4. customwas evaporated to dryness
5. stirringThis mixture was stirred for 2 hours at ambient temperature
6. stirringthe mixture was additionally stirred for 2 hours
7. extractionThe crude product was extracted with 5×200 ml of dichloromethane
8. extractionThe combined extract
9. dry with materialwas dried over Na2SO4
10. customevaporated to dryness
11. distillationFractional distillation
12. customgave
13. additiona mixture of two diastereomeric compounds, b.p. 108° C./3 mm Hg
14. customYield

ORD-Eintrag

ord-122d58c07bbf48deb88f6e71110178c3

Quelldatensatz

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07763562B2