1,2-Dibromoethane → HCID 46178908, compound

Temperature

-78 °C

n-Butyllithium (2.5 M in hexanes, 106 mL, 265 mmol) was added dropwise to a solution of diisopropylamine (37 mL, 264 mmol) in THF (0.8 L) over a period of 30 minutes, at −78° C., and under argon. The mixture was stirred for an additional 20 minutes at −78° C., and compound 15 (39 g, 226 mmol) was added. The mixture was allowed to warm to −20° C. for 30 minutes before 1,2-dibromoethane (47 mL, 545 mmol) was added to the mixture in one portion. After addition of the 1,2-dibromoethane, the reaction mixture was allowed to warm to 0° C. for 1.5 hours, and was then poured into a mixture of tert-butyl methyl ether (2 L) and ice cold aqueous NaHSO4 (1 M, 400 mL). The organic layer was separated, washed with a solution of aqueous NaHSO4 (1 M, 100 mL) and water (300 mL), and then washed multiple times with saturated aqueous NaHCO3 until the pH of the aqueous layer was 8 to 9. The organic layer was then washed with brine, dried over sodium sulfate, and concentrated to dryness to give crude 1vii. The crude product was distilled under high vacuum (1 mm Hg) and a fraction was collected at approximately 88° C. to 105° C. The product (13.5 g) was further purified by flash chromatography (silica gel) using dichloromethane/hexane 1:1 as the eluent. Appropriate fractions were combined and concentrated to afford pure compound 1vii as a clear oil (8.2 g, 13% yield). 1H NMR (CDCl3, δ): 0.88 (t), 1.29 (m), 1.45 (m), 1.45 (s), 1.59 (m), 1.91 (m,), 2.15 (m), 2.45 (m), 3.35 (m) and 3.40 (m) ppm; 13C NMR (CDCl3, δ): 13.9, 22.5, 28.1, 29.2, 31.1, 31.8, 35.2, 44.9, 80.5 and 174.5 ppm; MS (TOF) ESI+: [M+Na]+, 301.12, 303.12 Da.

1. additionwas added to the mixture in one portion
2. temperatureto warm to 0° C. for 1.5 hours
3. customThe organic layer was separated
4. washwashed with a solution of aqueous NaHSO4 (1 M, 100 mL) and water (300 mL)
5. washwashed multiple times with saturated aqueous NaHCO3 until the pH of the aqueous layer
6. washThe organic layer was then washed with brine
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated to dryness
9. customto give crude 1vii
10. distillationThe crude product was distilled under high vacuum (1 mm Hg)
11. customa fraction was collected at approximately 88° C. to 105° C
12. customThe product (13.5 g) was further purified by flash chromatography (silica gel)
13. concentrationconcentrated

ORD record

ord-a8695477d57a487e86e9c500c779a87f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653131B2