Allyl bromide → 2-allyl-2-(4-t-Butoxy-5-fluoro-3-methyl-2-pyridinyl)-acetaldehyde

To a solution of LDA (1.75 mmol, prepared from diisopropylamine (0.23 mL) and n-BuLi (2.5 M in hexanes, 0.70 mL) in THF (2.0 mL) at 0° C. was added N-(ethylidene)-cyclohexylamine (1.70 mmol, prepared in situ from acetaldehyde and cyclohexylamine) dropwise, and the reaction mixture was warmed to room temperature and stirred for 15 minutes. To this solution was added 4-t-butoxy-5-fluoro-3-methylpyridine (0.10 mL, 0.50 mmol) in THF (0.5 mL) dropwise and the mixture was stirred for 1 hour. To this mixture was added allyl bromide (0.15 mL, 1.75 mmol) dropwise., The exothermic reaction was stirred for 20 minutes, then quenched with water (3 mL). The mixture was then diluted with acetic acid (1M, 20 mL) and hexanes (20 mL) and stirred vigorously for 1 hour. The mixture was extracted with ether, and the organic layer was separated, washed with water, saturated NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by chromatography on silica gel, eluting with 5% to 10% ethyl acetate in hexanes, to afford the title compound (0.095 g, 73% yield) as an oil. MS 266 (M+H)+ ; 1H NMR (CDCl3) δ1.41 (d, 9H, J=1.1 Hz), 2.25 (s, 3H), 2.55-2.67 (m, 1H), 2.81-2.93 (m, 1H), 3.85 (m, 1H), 4.93-5.04 (m, 2H), 5.65-5.80 (m, 1H), 8.27 (d, 1H, J=1.8 Hz), 9.74 (m, 1H).

1. stirringthe mixture was stirred for 1 hour
2. custom, The exothermic reaction
3. stirringwas stirred for 20 minutes
4. customquenched with water (3 mL)
5. additionThe mixture was then diluted with acetic acid (1M, 20 mL) and hexanes (20 mL)
6. stirringstirred vigorously for 1 hour
7. extractionThe mixture was extracted with ether
8. customthe organic layer was separated
9. washwashed with water, saturated NaHCO3 and brine
10. dry with materialdried (MgSO4)
11. concentrationconcentrated
12. customThe residue was purified by chromatography on silica gel
13. washeluting with 5% to 10% ethyl acetate in hexanes

ORD-Eintrag

ord-62a6eb26a76042058d84a029ae623ca5

Quelldatensatz

uspto-grants-1998_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05789591