Methanesulfonyl chloride → 1-(1-Azidoethyl)-3-bromo-5-chloro-2-methoxy-4-methylbenzene

Temperature

0 °C

To a solution of 1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol (13.4 g, 47.9 mmol) in methylene chloride (150 mL), cooled at 0° C. was added N,N-diisopropylethylamine (14 mL, 80 mmol) followed by methanesulfonyl chloride (5.5 mL, 71 mmol). The mixture was stirred for 1 hour at 0° C. Water (100 mL) was added while cold. The organic layer was separated, washed with brine, dried over MgSO4, filtered and concentrated to dryness under reduced pressure. The resulting crude mesylate was dissolved in N,N-dimethylformamide (140 mL) and sodium azide (6.2 g, 96 mmol) was added. The reaction was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution, water and brine, dried over MgSO4, filtered and concentrated. The residue was purified on silica gel (eluting with 0-30% of ethyl acetate in hexanes) to afford the desired product (12.2 g, 82%). LCMS calculated for C10H11BrClO (M−N3)+: m/z=261.0, 263.0. found: 261.0, 263.0.

1. customThe organic layer was separated
2. washwashed with brine
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated to dryness under reduced pressure
6. dissolutionThe resulting crude mesylate was dissolved in N,N-dimethylformamide (140 mL)
7. stirringThe reaction was stirred at room temperature for 2 hours
8. washwashed with saturated sodium bicarbonate solution, water and brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified on silica gel (eluting with 0-30% of ethyl acetate in hexanes)

ORD record

ord-606e35122efa473a9f39c0bf510b9b72

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096600B2