6-Methylanthranilic acid → 2-Methyl-6-[4-(5-methyl-2-phenyl-oxazol-4-ylmethoxy)-benzenesulfonylamino]-benzoic acid

HRID 643985Notes

Reaction equation

HRID 643985 reaction equation
C(=O)(O)[O-].[Na+].[NH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[C:8]=1[C:9]([OH:11])=[O:10].[CH3:17][C:18]1[O:22][C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:20][C:19]=1[CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([S:37](Cl)(=[O:39])=[O:38])=[CH:33][CH:32]=1>C1COCC1.O>[CH3:16][C:12]1[CH:13]=[CH:14][CH:15]=[C:7]([NH:6][S:37]([C:34]2[CH:35]=[CH:36][C:31]([O:30][CH2:29][C:19]3[N:20]=[C:21]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[O:22][C:18]=3[CH3:17])=[CH:32][CH:33]=2)(=[O:38])=[O:39])[C:8]=1[C:9]([OH:11])=[O:10]

Participants

6

Reactant 3

HCID 1512106-Methylanthranilic acidHCID 516892Sodium BicarbonateHCID 210906794-(5-Methyl-2-phenyl-oxazol-4-ylmethoxy)-benzenesulfonyl chloride

Product 1

HCID 113520422-Methyl-6-[4-(5-methyl-2-phenyl-oxazol-4-ylmethoxy)-benzenesulfonylamino]-benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Sodium bicarbonate (159 mg, 1.89 mmol) and 2-amino-6-methylbenzoic acid (95.5 mg, 0.63 mmol) are dissolved in a mixture of 1 mL of THF and 1.5 mL of water and heated to 60° C. A solution of the title C compound, 4-(5-methyl-2-phenyl-oxazol-4-ylmethoxy)-benzenesulfonyl chloride (200 mg, 0.55 mmol) in 1 mL of THF is then added dropwise. The mixture is heated for an additional 2 h at 60° C., after which most of the THF is removed by passing a stream of nitrogen gas over the solution. The residue is partitioned between EtOAc and 1 N aqueous HCl. The organic phase is dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to give crude product which is purified by chromatography on silica gel with an EtOAc (15%)-hexane (85%) mixture (containing 0.5% formic acid) as the eluent to give 2-methyl-6-[4-(5-methyl-2-phenyl-oxazol-4-ylmethoxy)-benzenesulfonylamino]-benzoic acid as a white solid: m.p. 167-170° C.; ESI-MS 479 [M+1]+.

Workup

  1. temperatureThe mixture is heated for an additional 2 h at 60° C.
  2. customafter which most of the THF is removed
  3. customThe residue is partitioned between EtOAc and 1 N aqueous HCl
  4. dry with materialThe organic phase is dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give crude product which
  8. customis purified by chromatography on silica gel with an EtOAc (15%)-hexane (85%) mixture (containing 0.5% formic acid) as the eluent

Sources & evidence

ORD record
ord-fc4aae9e22b44da7b613dad9a540cc94
Source dataset
uspto-grants-2010_04
Patent number
US07700637B2

Reaction notes

Loading…