Lithium Hexamethyldisilazide → 2-(4-bromo-2-fluorophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide

HRID 15974ノート

反応式

HRID 15974 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:26])[C:11](=[O:25])[C:12]([CH3:24])=[CH:13][C:14]=2[C:15]([NH:17][O:18][CH2:19][CH2:20][O:21]C=C)=[O:16])=[C:4]([F:27])[CH:3]=1.BrC1C=CC(NC2N(C)C(=O)C(C)=CC=2C(OC)=O)=C(F)C=1.C(OCCON)=C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:26])[C:11](=[O:25])[C:12]([CH3:24])=[CH:13][C:14]=2[C:15]([NH:17][O:18][CH2:19][CH2:20][OH:21])=[O:16])=[C:4]([F:27])[CH:3]=1

参加物

6

反応物 4

HCID 2733832Lithium HexamethyldisilazideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 57636894Methyl 2-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylateHCID 866246672-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide

生成物 1

HCID 576369252-(4-bromo-2-fluorophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide収率 94%

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-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide: To a solution of methyl 2-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.060 g, 0.16 mmol) in THF (2 mL) was added O-(2-vinyloxy-ethyl)-hydroxylamine (0.042 ml, 0.41 mmol). The solution was cooled to 0° C. and lithium bis(trimethylsilyl)amide (0.81 ml, 0.81 mmol, 1 M solution in hexanes) was added dropwise. The reaction mixture was warmed to room temperature. After stirring for 35 minutes the reaction mixture was quenched by the addition of saturated NaHCO3 and partitioned between EtOAc and saturated NaCl. The layers were separated and the organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/MeOH, 20:1) gave 0.067 g (94%) pure desired product as an off-white crystalline solid.

後処理

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

出典と根拠

ORDレコード
ord-8e2a1c2f715b4bb09dc5c5042d5f396a
出典データセット
uspto-grants-2010_06
特許番号
US07732616B2

反応ノート

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