Lithium Hexamethyldisilazide → 4-Chloro-6-methoxynicotinimidamide hydrochloride

HRID 2044322Notes

Reaction equation

HRID 2044322 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([O:10][CH3:11])[CH:3]=1.[Li+].C[Si]([N-:17][Si](C)(C)C)(C)C>C1COCC1>[ClH:1].[Cl:1][C:2]1[C:7]([C:8]([NH2:17])=[NH:9])=[CH:6][N:5]=[C:4]([O:10][CH3:11])[CH:3]=1

Participants

4

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 582043184-Chloro-6-methoxypyridine-3-carbonitrile

Product 1

HCID 670506614-Chloro-6-methoxynicotinimidamide hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-chloro-6-methoxy-nicotinonitrile (10.1 g, 59.7 mmol) in THF (300 mL) at −78° C. was added LiHMDS (65.7 mL) dropwise and the reaction mixture stirred for 30 min before allowing to warm to RT and stirring for a further 1 h. The reaction was quenched by the addition of 1N HCl (to pH ˜1) and then extracted three times with ethyl acetate. The aqueous layer was concentrated in vacuo to give brown solid which was azeotroped with toluene to give the title compound as a tan solid. Mixture with ammonium chloride, 72% title compound by weight. (15.2 g, 83%). 1H NMR 400 MHz (DMSO-d) δ: 9.68 (4H, d, J=15.79 Hz), 8.46 (1H, s), 7.47 (5H, t, J=50.66 Hz), 7.27 (1H, s), 3.95 (3H, s).

Workup

  1. stirringstirring for a further 1 h
  2. customThe reaction was quenched by the addition of 1N HCl (to pH ˜1)
  3. extractionextracted three times with ethyl acetate
  4. concentrationThe aqueous layer was concentrated in vacuo
  5. customto give brown solid which
  6. customwas azeotroped with toluene

Sources & evidence

ORD record
ord-9147e553ffb6432b99dca7961beed26b
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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