Pyridine, 2,4,6-trichloro- → HCID 90016257, compound

HRID 1057026Notes

Reaction equation

HRID 1057026 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[C:4]([Cl:9])[N:3]=1.[O:10]1[CH2:15][CH2:14][CH:13]([C:16]#[N:17])[CH2:12][CH2:11]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:13]2([C:16]#[N:17])[CH2:14][CH2:15][O:10][CH2:11][CH2:12]2)[CH:5]=[C:4]([Cl:9])[N:3]=1

Participants

5

Reactant 3

HCID 27665Pyridine, 2,4,6-trichloro-HCID 2733832Lithium HexamethyldisilazideHCID 11815837Oxane-4-carbonitrile

Product 1

HCID 90016257HCID 90016257, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 2,4,6-trichloropyridine (4.65 g, 24.7 mmol) and tetrahydropyran-4-carbonitrile (2.29 g, 20.6 mmol) in THF (100 mL, 0.2 M) and under nitrogen at −78° C. was added lithium bis(trimethylsilyl)amide (29 mL, 29 mmol, 1.0 M in THF) and after 5 min, the cooling bath was removed. After stirring a further 40 min, the reaction was quenched by the addition of sat. aq. NH4Cl and then concentrated. The mixture was extracted with CH2Cl2 and organics dried over MgSO4. Following concentration, the residue was purified by flash column chromatography (100:0-70:30 heptanes/EtOAc) but care needed to be taken to prevent compound precipitation on the column. After purification, 4-(2,6-dichloro-4-pyridyl)tetrahydropyran-4-carbonitrile was obtained a white solid (3.75 g, 71%); 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J=0.6 Hz, 2H), 4.17-4.05 (m, 2H), 3.93-3.84 (m, 2H), 2.15-1.99 (m, 4H).

Workup

  1. customthe cooling bath was removed
  2. customthe reaction was quenched by the addition of sat. aq. NH4Cl
  3. concentrationconcentrated
  4. extractionThe mixture was extracted with CH2Cl2
  5. dry with materialorganics dried over MgSO4
  6. concentrationconcentration
  7. customthe residue was purified by flash column chromatography (100:0-70:30 heptanes/EtOAc)
  8. customcompound precipitation on the column
  9. customAfter purification

Sources & evidence

ORD record
ord-813a6ae3dd064eee8f18ab8d237d0ce9
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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