3-(Chloromethyl)pyridine hydrochloride → HCID 19708731, compound

HRID 725792Notes

Reaction equation

HRID 725792 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([S:12]([N:15]2[CH2:20][CH:19]3[CH2:21][CH:16]2[CH2:17][S:18]3)(=[O:14])=[O:13])[CH:3]=1.Cl.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29]Cl)[CH:24]=1.[H-].[Na+]>CN(C=O)C>[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][O:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[C:4]([S:12]([N:15]3[CH2:20][CH:19]4[CH2:21][CH:16]3[CH2:17][S:18]4)(=[O:14])=[O:13])[CH:3]=2)[CH:24]=1

Participants

5

Reactant 3

HCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 24758Sodium hydrideHCID 19708720HCID 19708720, compound

Product 1

HCID 19708731HCID 19708731, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

The product from Example 62 (66 mg, 0.20 mmol), 3-picolylchloride hydrochloride (40 mg, 0.20 mmol and a crystal of KI were combined in DMF (30 ml). Sodium hydride (41 mg, 1.1 mmol, a 60% dispersion in oil) was added and the mixture was stirred at 90° C. for 15 hr. At this time the solvent was evaporated under reduced pressure and the residue was partitioned between 1N aq KOH and CHCl3. The CHCl3 phase was dried (Na2SO4) and concentrated and the residue was purified by flash chromatography using 5% acetone in CHCl3. The pure product was obtained as a tan foam (49 mg, 58% yield): 1H NMR (CDCl3) δ 1.52 (1H, d, J=10.57 Hz, 1/2 CH2), 1.69 (1H, J=10.74 Hz, 1/2 CH2), 1.81 (1H, br s, CH), 2.91 (1H, dd, J=10.12, 2.53, 1/2 CH2), 3.09 (1H, d, J=10.15 Hz, 1/2 CH2), 3.50 (2H, m, CH2), 3.61 (1H, dd, J=10.21, 1.14 Hz, CH), 4.62 (2H, s, CH2Ar), 7.19 (1H, d, J=1.39 Hz, ArH). 7.39 (1H, dd, J=11.61, 4.87 Hz, 7.60-7.69 (2H, m, ArH), 7.82-7.98 (2H, m, ArH), 8.01 (1H, s, ArH), 8.30-8.38 (1H, m, ArH), 8.68 (1H, dd, J=10.19, 1.35 Hz, ArH), 8.81 (1H, d, J=1.86 Hz, ArH).

Workup

  1. customAt this time the solvent was evaporated under reduced pressure
  2. customthe residue was partitioned between 1N aq KOH and CHCl3
  3. dry with materialThe CHCl3 phase was dried (Na2SO4)
  4. concentrationconcentrated
  5. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-95c5c0b0af9a4e28a43acbf97bd066d0
Source dataset
uspto-grants-1998_01
Patent number
US05707985

Reaction notes

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