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

HRID 481807Notes

Reaction equation

HRID 481807 reaction equation
[Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.[Li]CCCC.C(=N[CH:24]1[CH2:29][CH2:28]C[CH2:26][CH2:25]1)C.[C:30]([O:34][C:35]1[C:40]([F:41])=[CH:39][N:38]=[CH:37][C:36]=1[CH3:42])([CH3:33])([CH3:32])[CH3:31].C(Br)C=C.C1C[O:50]CC1>>[CH2:24]([CH:29]([C:37]1[C:36]([CH3:42])=[C:35]([O:34][C:30]([CH3:33])([CH3:32])[CH3:31])[C:40]([F:41])=[CH:39][N:38]=1)[CH:28]=[O:50])[CH:25]=[CH2:26]

Participants

8

Reactant 7

HCID 7841Allyl bromideHCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 2724682Lithium diisopropylamideHCID 10964544N-cyclohexylethanimineHCID 190671094-t-Butoxy-5-fluoro-3-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 190670972-allyl-2-(4-t-Butoxy-5-fluoro-3-methyl-2-pyridinyl)-acetaldehydeYield 73%

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-62a6eb26a76042058d84a029ae623ca5
Source dataset
uspto-grants-1998_08
Patent number
US05789591

Reaction notes

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