Dimethylformamide → Methyl 2-(6-chloro-5-fluoropyridin-3-yloxy)-4-fluorobenzoate

HRID 573112

反応式

HRID 573112 の反応式
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC([O-])(C)C.[K+].F[C:17]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20].CN(C)C=O>CC1CCCO1.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:17]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:18]=2[C:19]([O:21][CH3:22])=[O:20])=[CH:4][C:3]=1[F:9]

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 2782897Methyl 2,4-DifluorobenzoateHCID 23665647Potassium tert-butoxideHCID 404247372-Chloro-3-fluoro-5-hydroxypyridine

生成物 1

HCID 86642876Methyl 2-(6-chloro-5-fluoropyridin-3-yloxy)-4-fluorobenzoate

試薬・触媒・溶媒 2

HCID 73012-Methyltetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 6-chloro-5-fluoropyridin-3-ol (0.977 g) in 2-methyltetrahydrofuran (12 mL) was added potassium 2-methylpropan-2-olate (1.0M in tetrahydrofuran, 7.28 mL). After stirring for 15 minutes at room temperature, methyl 2,4-difluorobenzoate (1.710 g) was added as a solution in 2-methyltetrahydrofuran (2 mL) followed by N,N-dimethylformamide (2 mL) then the reaction was heated to 75° C. under a nitrogen atmosphere. After stirring overnight the reaction was cooled, diluted with ethyl acetate (100 mL) and washed with water (50 mL) and brine (50 mL), dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (GraceResolv 40 g) eluting with a gradient of 2% to 15% ethyl acetate/hexanes gave the title compound.

後処理

  1. temperaturethe reaction was heated to 75° C. under a nitrogen atmosphere
  2. stirringAfter stirring overnight the reaction
  3. temperaturewas cooled
  4. washwashed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washSilica gel chromatography (GraceResolv 40 g) eluting with a gradient of 2% to 15% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-83abc5fa911a4bf9b6f6b3b079582642
出典データセット
uspto-grants-2015_05
特許番号
US09029404B2

関連ノート

読み込み中…