Sodium hydride → 5-[(2-amino-5H-thiazol-5-yl)oxy]-2-fluoro-benzoic acid methyl ester
Reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([OH:12])[CH:9]=[CH:8][C:7]=1[F:13].[NH2:15][C:16]1[S:17][C:18](Br)=[CH:19][N:20]=1>O1CCCC1>[CH3:3][O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([O:12][CH:18]2[S:17][CH:16]([NH2:15])[N:20]=[CH:19]2)[CH:9]=[CH:8][C:7]=1[F:13]Participants
Procedure
To a solution of sodium hydride (1.7 g, 44.11 mmol) in tetrahydrofuran (50 mL) was added solution of 2-fluoro-5-hydroxy benzoic acid methyl ester (5 g, 29.41 mmol) in tetrahydrofuran (50 mL) under argon atmosphere and stirred for 15 minutes. A solution of 2-amino-5-bromothiazole (5.2 g, 29.41 mmol) in tetrahydrofuran (47 mL) was added dropwise over a period of 30 min and stirred at room temperature for 4 hrs. Reaction mixture was poured into ice cold water (300 mL) extracted with ethyl acetate (3×200 mL), combined organic layers were washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Crude compound was purified by silica gel column chromatography using 40% ethyl acetate in hexane as eluent to afford pure 5-[(2-amino-5H-thiazol-5-yl)oxy]-2-fluoro-benzoic acid methyl ester. (2.5 g).
Workup
- stirringstirred at room temperature for 4 hrs
- customReaction mixture
- extractionextracted with ethyl acetate (3×200 mL)
- washwere washed with brine
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customCrude compound was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-72695a21260345c1bbe944973320cd06
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340506B2
Reaction notes
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