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

Temperature

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 with vigorous stirring over 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 the 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 record

ord-ef60f981e5854df38b7deb25a349139c

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07446216B2