Lithium Hexamethyldisilazide → 2-(3,5-Dichloro-pyridin-4-yl)-1-(2,3,4-trimethoxy-phenyl)-ethanone

HRID 456030Notes

Reaction equation

HRID 456030 reaction equation
[CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[C:11]([O:15][CH3:16])[CH:10]=[CH:9][C:4]=1[C:5]([O:7]C)=O.[Cl:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22]([Cl:25])[C:23]=1[CH3:24].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22]([Cl:25])[C:23]=1[CH2:24][C:5]([C:4]1[CH:9]=[CH:10][C:11]([O:15][CH3:16])=[C:12]([O:13][CH3:14])[C:3]=1[O:2][CH3:1])=[O:7]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 109538273,5-Dichloro-4-methylpyridineHCID 13940801Methyl 2,3,4-trimethoxybenzoate

Product 1

HCID 227340502-(3,5-Dichloro-pyridin-4-yl)-1-(2,3,4-trimethoxy-phenyl)-ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2,3,4-trimethoxybenzoate from preparation 1 (2.7 g, 10 mmol) and 3,5-dichloro-4-methylpyridine (prepared according to literature procedures) was dissolved in dry THF (40 mL). The reaction was cooled on ice and treated dropwise (during 5 minutes) with 1M lithium bis(trimethylsilyl)amide (12 mL, 12 mmol). After 1.5 hours at 0° C. the reaction was quenched with NH4Cl (sat, 100 mL). The organic products were extracted with EtOAc (2×100 mL), and the combined organic phases washed with NaCl (sat, 100 mL). The organic phase was dried over Na2SO4, evaporated in vacuo and purified by flash chromatography using a gradient of EtOAc in heptane as eluent. 2-(3,5-Dichloro-pyridin-4-yl)-1-(2,3,4-trimethoxy-phenyl)-ethanone was obtained as a white solid. 1H NMR (CDCl3) δ=8.43 (2H, s), 7.55 (1H, d), 6.69 (1H, d), 4.61 (2H, s), 4.02 (3H, s), 3.87 (3H, s), 3.84 (3H, s). Yield 2.3 g (65%).

Workup

  1. temperatureThe reaction was cooled on ice
  2. customAfter 1.5 hours at 0° C. the reaction was quenched with NH4Cl (sat, 100 mL)
  3. extractionThe organic products were extracted with EtOAc (2×100 mL)
  4. washthe combined organic phases washed with NaCl (sat, 100 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. customevaporated in vacuo
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-7ce48ea990424bbda3fd79438b889417
Source dataset
uspto-grants-2013_07
Patent number
US08497380B2

Reaction notes

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