HCID 22941953, compound → HCID 22941957, compound

HRID 361595Notes

Reaction equation

HRID 361595 reaction equation
[N:1]1([CH2:6]/[CH:7]=[C:8](/[C:16]2[N:21]=[C:20](/[CH:22]=[CH:23]/[CH:24]=[O:25])[CH:19]=[CH:18][CH:17]=2)\[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:26][Mg]Br>C1COCC1>[N:1]1([CH2:6]/[CH:7]=[C:8](/[C:16]2[N:21]=[C:20](/[CH:22]=[CH:23]/[CH:24]([OH:25])[CH3:26])[CH:19]=[CH:18][CH:17]=2)\[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 22941953HCID 22941953, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 22941957HCID 22941957, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 3-(6-[3-pyrrolidin-1-yl-1-{4-tolyl}-prop-1E-enyl]-pyridin-2-yl)-prop-2E-enal (1.41 g, 4.24 mmol) in anhydrous THF (50 ml) at -78° C. was treated dropwise with a solution of methyl magnesium bromide (1.56 ml, 3.0M in diethylether, 4.67 mmol). The reaction mixture was allowed to warm slowly to room temperature (~2 hours). The reaction was quenched with water (3 ml) and THF removed under reduced pressure. The residue was taken up in 1M HCl and then basified with solid sodium bicarbonate to pH 8. The product was extracted with ethyl acetate (×3). The organics were combined, dried over sodium sulphate, filtered and concentrated under reduced pressure. The product was purified by column chromatography eluting with 5% methanol in DCM. Product containing fractions were combined and solvent removed to provide 4-(6-[3-pyrrolidin-1-yl-1-{4-tolyl}-prop-1E-enyl]-pyridin-2-yl)-but-3E-en-2-ol as a pale brown foam (544 mg, 37%). 1H-NMR; δ (CDCl3), 7.43 (1H, t, J=7.8 Hz), 7.24-7.18 (3H, m), 7.11-7.06 (3H, m), 6.94 (1H, dd, J=15.6 and 5.8 Hz), 6.71-6.64 (2H, m), 4.60-4.55 (1H, m), 3.23 (2H, d, J=7.0 Hz), 2.58 (4H, bs), 2.41 (3H, s), 1.82-1.77 (4H, m), 1.41 (3H, d, J=6.5 Hz).

Workup

  1. customThe reaction was quenched with water (3 ml) and THF
  2. customremoved under reduced pressure
  3. extractionThe product was extracted with ethyl acetate (×3)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe product was purified by column chromatography
  8. washeluting with 5% methanol in DCM
  9. additionProduct containing fractions
  10. customsolvent removed

Sources & evidence

ORD record
ord-4e1fc61f18c54265ae5b4eb1271ca170
Source dataset
uspto-grants-1999_02
Patent number
US05866588

Reaction notes

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