Sodium hydride → 3-[5-Fluoro-3-(tetrahydro-pyran-4-YL)-pyridin-2-yloxy]-cyclobutanecarboxylic acid methyl ester

HRID 1846787노트

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HRID 1846787 반응식
[OH:1][CH:2]1[CH2:5][CH:4]([C:6]([O:8][CH3:9])=[O:7])[CH2:3]1.[H-].[Na+].F[C:13]1[C:18]([CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[CH:17][C:16]([F:25])=[CH:15][N:14]=1>CN(C=O)C>[CH3:9][O:8][C:6]([CH:4]1[CH2:5][CH:2]([O:1][C:13]2[C:18]([CH:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[CH:17][C:16]([F:25])=[CH:15][N:14]=2)[CH2:3]1)=[O:7]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 12815112Cyclobutanecarboxylic acid, 3-hydroxy-, methyl esterHCID 585485232,5-Difluoro-3-(tetrahydro-pyran-4-YL)-pyridine

생성물 1

HCID 585486433-[5-Fluoro-3-(tetrahydro-pyran-4-YL)-pyridin-2-yloxy]-cyclobutanecarboxylic acid methyl ester수율 114.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

To a solution of methyl 3-hydroxycyclobutanecarboxylate (1.2 g, 9.0 mmol) in DMF (20 mL) was added sodium hydride (60% wt in mineral oil) (1.8 g, 45 mmol) at RT. The mixture was stirred for 1 h and then 2,5-difluoro-3-(tetrahydro-pyran-4-yl)-pyridine (1.8 g, 9.0 mmol) was added. The reaction mixture was heated to 60° C. for 3 h and then quenched with saturated NH4Cl. The solution was diluted with EtOAc and water and extracted with EtOAc (2×10 mL). The organic extracts were combined, washed with brine (10 mL), dried over MgSO4, filtered, and concentrated to get a residue, which was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes) to give the product (3.2 g) as yellow oil.

후처리

  1. customquenched with saturated NH4Cl
  2. additionThe solution was diluted with EtOAc and water
  3. extractionextracted with EtOAc (2×10 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto get a residue, which
  9. customwas purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-bd943488edc349adada2d4b197862f21
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952037B2

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