Lithium → 4-{[(2,4-Dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}-3-fluorobenzoic acid

HRID 401758Notes

Reaction equation

HRID 401758 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[CH:10][N:11]=1.[Li].Cl[S:20]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][C:24]=1[F:32])(=[O:22])=[O:21]>C1COCC1.[Cl-].[Na+].O>[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][N:6]([C:7]1[S:8][CH:9]=[CH:10][N:11]=1)[S:20]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][C:24]=1[F:32])(=[O:21])=[O:22]

Participants

6

Reactant 3

HCID 3028194LithiumHCID 113109714-(Chlorosulfonyl)-3-fluorobenzoic acidHCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amine

Product 1

HCID 685355954-{[(2,4-Dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}-3-fluorobenzoic acidYield 17.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

N-(2,4-dimethoxybenzyl)-1,3-thiazol-2-amine (Preparation 6, 2.34 g, 9.35 mmol, 0.95 eq) was suspended in THF (20 ml) and stirred at 0° C. for 10 minutes. 1,1,1,3,3,3-Hexanemethyldisilazane lithium salt (LiHMDS, 1M in THF, 19.5 ml, 20 mmol, 2.0 eq) was added dropwise maintaining the temperature below 30° C. and the reaction mixture stirred for a further 30 minutes. A solution of 4-(chlorosulfonyl)-3-fluorobenzoic acid (Preparation 9, 2.35 g, 9.85 mmol, 1 eq) in THF (15 ml) was added dropwise maintaining the reaction temperature below 30° C. and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was diluted with brine (10 ml), extracted into ethyl acetate (10 ml), dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was slurried in t-butylmethyl ether and stirred at room temperature for 72 hours. The resulting solid was collected by filtration to yield the title compound as a beige solid (744 mg, 1.64 mmol, 17%).

Workup

  1. temperaturemaintaining the temperature below 30° C.
  2. stirringthe reaction mixture stirred for a further 30 minutes
  3. temperaturemaintaining the reaction temperature below 30° C.
  4. stirringthe reaction mixture stirred at room temperature for 2 hours
  5. extractionextracted into ethyl acetate (10 ml)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. stirringstirred at room temperature for 72 hours
  10. filtrationThe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-d927bac505804709a7b72ecae689bb12
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Reaction notes

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