Lithium Hexamethyldisilazide → 2-(2-Fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-hydroxyethoxy)-amide

HRID 15940

反応式

HRID 15940 の反応式
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][C:13](=[O:16])[N:12]([CH3:17])[C:11]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=1[F:26])=[O:9])=C.COC(C1C=CC(=O)N(C)C=1NC1C=CC(C)=CC=1F)=O.C(OCCON)=C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][C:13](=[O:16])[N:12]([CH3:17])[C:11]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=1[F:26])=[O:9]

参加物

6

反応物 4

HCID 2733832Lithium HexamethyldisilazideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 598435712-(2-Fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl esterHCID 866723222-(2-Fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amide

生成物 1

HCID 112329322-(2-Fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-hydroxyethoxy)-amide収率 77%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

Preparation of 2-(2-fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amide: To a solution of 2-(2-fluoro-4-methylphenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester (0.050 g, 0.17 mmol) in THF (1.5 mL) under N2 was added O-(2-vinyloxy-ethyl)-hydroxylamine (0.044 g, 0.43 mmol). The solution was cooled to 0° C. and lithium bis(trimethylsilyl)amide (0.86 mL, 0.86 mmol, 1 M solution in hexanes) was added dropwise. The reaction mixture was warmed to room temperature. After stirring for 40 minutes, the reaction mixture was quenched by the addition of NaHCO3 and partitioned between EtOAc and saturated NaCl. The layers were separated and the aqueous layer was reextracted with EtOAc. The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/methanol, 20:1) gave 0.048 g (77%) pure desired product as an off-white foamy solid.

後処理

  1. temperatureThe reaction mixture was warmed to room temperature
  2. customthe reaction mixture was quenched by the addition of NaHCO3
  3. custompartitioned between EtOAc and saturated NaCl
  4. customThe layers were separated
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (methylene chloride/methanol, 20:1)

出典と根拠

ORDレコード
ord-dc7756c0c1a64ef594ac7b5868cedbe4
出典データセット
uspto-grants-2010_06
特許番号
US07732616B2

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