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

HRID 573112

반응식

HRID 573112 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 73012-Methyltetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-83abc5fa911a4bf9b6f6b3b079582642
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029404B2

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