3-Hydroxyanthranilic Acid → Methyl 2-(4-chlorophenyl)benzoxazole-4-carboxylate

HRID 969822Notes

Reaction equation

HRID 969822 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=[O:6])[C:3]=1[NH2:11].[Cl:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1.[CH3:22]CN(C(C)C)C(C)C.CI>CN(C=O)C.C(OCC)(=O)C.Cl>[Cl:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]2[O:1][C:2]3[C:3](=[C:4]([C:5]([OH:7])=[O:6])[CH:8]=[CH:9][CH:10]=3)[N:11]=2)=[CH:15][CH:14]=1.[Cl:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]2[O:18][C:2]3[C:3](=[C:4]([C:5]([O:7][CH3:22])=[O:6])[CH:8]=[CH:9][CH:10]=3)[N:11]=2)=[CH:15][CH:14]=1

Participants

9

Reactant 4

HCID 863-Hydroxyanthranilic AcidHCID 6328Methyl iodideHCID 85014-Chlorobenzoyl chlorideHCID 81531Diisopropylethylamine

Product 2

HCID 596258542-(4-Chlorophenyl)benzoxazole-4-carboxylic acidHCID 68459315Methyl 2-(4-chlorophenyl)benzoxazole-4-carboxylateYield 30%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(4-Chlorophenyl)benzoxazole-4-carboxylic acid was prepared from 3-hydroxyanthranilic acid and 4-chlorobenzoyl chloride using the method described in Step A of Example 1. This crude material (2.90 g, 10.6 mmol) was directly dissolved in DMF (40 mL), DIPEA (5.46 g, 42.4 mmol) and methyl iodide (5.93 g, 42.4 mmol) added and the reaction stirred at room temperature for 18 h. After this time the reaction was diluted with ethyl acetate (100 mL) and 2 N HCl (50 mL). The organic layer was separated and then washed with 2 N HCl (25 mL), water (50 mL) and brine (50 mL). The organic layer was then dried over sodium sulfate, filtered and concentrated to dryness to yield light yellow oil. This material was purified using silica gel chromatography to afford 0.532 g (30% yield) of methyl 2-(4-chlorophenyl)benzoxazole-4-carboxylate as a white solid: 1H NMR (300 MHz, CDCl3) δ 8.28 (dd, J=6.9, 1.8 Hz, 2H), 8.04 (d, J=8.1 Hz, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.52 (d, J=8.7 Hz, 2H), 7.43 (t, J=7.8 Hz, 1H), 4.06 (s, 3H); MS (ESI) m/z 288 [M+H]+

Workup

  1. customThe organic layer was separated
  2. washwashed with 2 N HCl (25 mL), water (50 mL) and brine (50 mL)
  3. dry with materialThe organic layer was then dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customto yield light yellow oil
  7. customThis material was purified

Sources & evidence

ORD record
ord-c9915bb799514e78a4f761b8686333f9
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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