2-Amino-4-chlorophenol → 5-Chloro-2-(3-methoxy-4-pyridin-2-ylphenyl)-1,3-benzoxazole

HRID 7772

Reaction equation

HRID 7772 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[C:6]([OH:8])=O.[NH2:18][C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1O>O>[Cl:25][C:23]1[CH:22]=[CH:21][C:20]2[O:8][C:6]([C:5]3[CH:9]=[CH:10][C:11]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=4)=[C:3]([O:2][CH3:1])[CH:4]=3)=[N:18][C:19]=2[CH:24]=1

Participants

4

Reactant 2

HCID 72652-Amino-4-chlorophenolHCID 219565153-Methoxy-4-(pyridin-2-yl)benzoic acid

Product 1

HCID 102866725-Chloro-2-(3-methoxy-4-pyridin-2-ylphenyl)-1,3-benzoxazole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3-Methoxy-4-pyridin-2-yl benzoic acid (500 mg, 2.2 mmol), 2-amino-4-chlorophenol (620 mg, 4.3 mmol) and trimethyl silylpolyphosphate (2 mL) was heated to 180° C. overnight under argon. To the cooled reaction mixture, water (100 mL) was added and extracted with EtOAc (4×20 mL). Set aside organic layer. Filtered aqueous layer through Celite pad and basified filtrate to pH 9 (solid NaHCO3). Extracted with EtOAc (2×30 mL), combined all organic layers and concentrated in vacuo. The resulting orange oil was purified by flash chromatography using a gradient elution of 15:85 ethyl acetate:hexane to 1:1 ethyl acetate:hexane to give the desired intermediate, 5-chloro-2-(3-methoxy-4-pyridin-2-ylphenyl)-1,3-benzoxazole as a colorless solid.

Workup

  1. additionwas added
  2. extractionextracted with EtOAc (4×20 mL)
  3. extractionExtracted with EtOAc (2×30 mL)
  4. concentrationconcentrated in vacuo
  5. customThe resulting orange oil was purified by flash chromatography
  6. washa gradient elution of 15:85 ethyl acetate

Sources & evidence

ORD record
ord-14747b92927c4a008bd0c9dd2379904e
Source dataset
uspto-grants-2006_08
Patent number
US07087601B2

Linked notes

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