Sodium Carbonate → HCID 10152715, compound

HRID 854559Notes

Reaction equation

HRID 854559 reaction equation
C([O:3][C:4](=[O:29])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][CH2:14][C:15]2[S:19][C:18]([C:20]3[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=3)=[N:17][C:16]=2[CH3:27])=[CH:9][C:8]=1[CH3:28])C.[F:30][C:31]([F:42])([F:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C>[CH3:28][C:8]1[CH:9]=[C:10]([S:13][CH2:14][C:15]2[S:19][C:18]([C:20]3[CH:21]=[CH:22][C:23]([C:35]4[CH:36]=[CH:37][C:32]([C:31]([F:42])([F:41])[F:30])=[CH:33][CH:34]=4)=[CH:24][CH:25]=3)=[N:17][C:16]=2[CH3:27])[CH:11]=[CH:12][C:7]=1[O:6][CH2:5][C:4]([OH:3])=[O:29]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 9957299HCID 9957299, compound

Product 1

HCID 10152715HCID 10152715, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 21863594Toluene ethanolSolvent

Procedure

To a solution of {4-[2-(4-Bromo-phenyl)-4-methyl-thiazol-5-ylmethylsulfanyl]-2-methyl-phenoxy}-acetic acid ethyl ester (53 mg, 0.1076 mmol) in toluene:ethanol (1:1, 2.0 mL) is added palladium tetrakis triphenylphosphine (5.0 mg, 0.0053 mmol), 4-(trifluoromethyl)-phenyl boronic acid (22.5 mg, 0.1184 mmol), and a solution of sodium carbonate (0.216 mL, 1.0M in water, 0.216 mmol). The reaction is purged with nitrogen and heated to reflux. The reaction is monitored by HPLC, and upon completion is allowed to cool to room temperature. The reaction is diluted with EtOAc and then washed with 0.1N sodium hydroxide, water, and brine. The organic layer is dried over anhydrous sodium sulfate, then concentrated. The product is purified by flash column chromatography. The pure ester compound is then diluted with THF and 1N sodium hydroxide is added. The reaction is allowed to stir at room temperature, and monitored by TLC. Upon completion, 1N hydrochloric acid is added to neutralize the solution. The reaction is diluted with EtOAc and then washed with water. The organic layer is dried over anhydrous sodium sulfate and concentrated to the pure acid, 50 mg or 94% yield. MS (ES): 530.7 (M++1), the structure is also confirmed by proton NMR.

Workup

  1. customThe reaction is purged with nitrogen
  2. temperatureheated to reflux
  3. additionThe reaction is diluted with EtOAc
  4. washwashed with 0.1N sodium hydroxide, water, and brine
  5. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe product is purified by flash column chromatography
  8. additionThe pure ester compound is then diluted with THF and 1N sodium hydroxide
  9. additionis added
  10. additionUpon completion, 1N hydrochloric acid is added
  11. additionThe reaction is diluted with EtOAc
  12. washwashed with water
  13. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  14. concentrationconcentrated to the pure acid, 50 mg or 94% yield

Sources & evidence

ORD record
ord-23929df2d8044df8be5d8ee94b804222
Source dataset
uspto-grants-2007_08
Patent number
US07259175B2

Reaction notes

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