1-Bromo-3-methylbutane → HCID 25259505, compound

Temperature

42.5 °C

To a solution of lithium bis(trimethylsilyl)amide (278.57 g, 1.66 mol) in tetrahydrofuran (700 mL) was added 2-phenyl propionic acid (100.0 g, 0.666 mol) over 40 minutes maintaining the temperature below 15° C. The solution was warmed 40-45° C. for 20 minutes, then cooled below 25° C. and 1-bromo-3-methylbutane (156.0 g, 1.03 mol) was added. The reaction mixture was heated to 50° C. for 10 h, then was cooled to RT, and concentrated to a thick sludge. Methyl tert-butyl ether (900 mL) and water (1100 mL) were added, and the layers were separated. The organic phase was extracted with H2O (200 mL). The combined aqueous phases were treated with 3 M HCl (520 mL) to adjust the pH to approximately 2. The product was extracted with ethyl acetate (1000 mL) and the organic layer was concentrated to a thick oil to give the title compound. The crude oil (assayed for 136.99 g of Example 39-1, 95.3% assay yield) was used directly.

1. temperaturemaintaining the temperature below 15° C
2. temperaturecooled below 25° C.
3. temperatureThe reaction mixture was heated to 50° C. for 10 h
4. temperaturewas cooled to RT
5. concentrationconcentrated to a thick sludge
6. additionMethyl tert-butyl ether (900 mL) and water (1100 mL) were added
7. customthe layers were separated
8. extractionThe organic phase was extracted with H2O (200 mL)
9. additionThe combined aqueous phases were treated with 3 M HCl (520 mL)
10. extractionThe product was extracted with ethyl acetate (1000 mL)
11. concentrationthe organic layer was concentrated to a thick oil

ORD record

ord-a9b863c46284400fb31e24a55f532050

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538105B2