Sodium hydride → Ethyl 3-[4-(2-aminothiazol-5-yl)oxyphenyl]isoxazole-5-carboxylate

HRID 524416Notes

Reaction equation

HRID 524416 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[C:21]1[S:25][C:24]([NH2:26])=[N:23][CH:22]=1>C1COCC1>[NH2:26][C:24]1[S:25][C:21]([O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[O:10][N:9]=3)=[CH:6][CH:7]=2)=[CH:22][N:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 436002-Thiazolamine, 5-bromo-HCID 136133842Ethyl 3-(4-hydroxyphenyl)isoxazole-5-carboxylate

Product 1

HCID 86669547Ethyl 3-[4-(2-aminothiazol-5-yl)oxyphenyl]isoxazole-5-carboxylateYield 20.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of ethyl 3-(4-hydroxyphenyl)isoxazole-5-carboxylate (0.97 g, 4.16 mmol) in dry THF, sodium hydride (60%, 0.25 g, 6.09 mmol) was added at room temperature and stirred for 10 min. 5-bromothiazol-2-amine (0.5 g, 2.77 mmol) dissolved in 10 mL dry THF was added and continued to stir for additional 1 hr. Reaction mixture was poured on ice cold water and extracted with ethyl acetate (50 mL×3). The combined organic layer was washed with water, brine and dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude material which was purified by silica gel column chromatography using 40-50% ethyl acetate in hexane to provide the title compound (0.19 g).

Workup

  1. additionwas added
  2. stirringto stir for additional 1 hr
  3. customReaction mixture
  4. additionwas poured on ice cold water
  5. extractionextracted with ethyl acetate (50 mL×3)
  6. washThe combined organic layer was washed with water, brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto get crude material which
  11. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f3ba39627efa4939a6cfedd3dba5c9ec
Source dataset
uspto-grants-2016_05
Patent number
US09340506B2

Reaction notes

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