Lithium Hexamethyldisilazide → 2-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide

HRID 2068921Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:11]([CH3:22])[C:12](=[O:21])[C:13]([CH3:20])=[CH:14][C:15]=1[C:16]([O:18]C)=O.[CH:23]([O:25][CH2:26][CH2:27][O:28][NH2:29])=[CH2:24].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:11]([CH3:22])[C:12](=[O:21])[C:13]([CH3:20])=[CH:14][C:15]=1[C:16]([NH:29][O:28][CH2:27][CH2:26][O:25][CH:23]=[CH2:24])=[O:18]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 2-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.500 g, 1.20 mmol) in THF (60 mL) was added O-(2-vinyloxy-ethyl)-hydroxylamine (0.149 g, 1.44 mmol). The solution was cooled to 0° C. and lithium bis(trimethylsilyl)amide (4.81 ml, 4.81 mmol) (1 M solution in hexanes) was added dropwise. The reaction mixture was warmed to room temperature. After stirring for 10 minutes the reaction mixture was quenched by the addition of 1 M HCl and partitioned between EtOAc and saturated NaCl. The layers were separated and the organic layer was dried (Na2SO4) and concentrated under reduced pressure to yield a crude yellow solid that was used without purification in the next step.

Workup

temperatureThe reaction mixture was warmed to room temperature
customwas quenched by the addition of 1 M HCl
custompartitioned between EtOAc and saturated NaCl
customThe layers were separated
dry with materialthe organic layer was dried (Na2SO4)
concentrationconcentrated under reduced pressure
customto yield a crude yellow solid that
customwas used without purification in the next step

Sources & evidence

ORD record: ord-ce888d12372149c3a9f285394a719c7f
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299076B2

Reaction notes

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