Potassium Carbonate → 2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)-2-methylpropanoic acid

HRID 68619

Reaction equation

HRID 68619 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([CH:25]=[CH:26][C:27]=2[OH:28])[CH2:12][N:13]([CH3:24])[S:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:6]=[CH:7][CH:8]=1.C([O:35][C:36](=[O:41])[C:37](Br)([CH3:39])[CH3:38])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:30][C:2]([F:1])([F:29])[C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([CH2:12][N:13]([CH3:24])[S:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH:25]=[CH:26][C:27]=2[O:28][C:37]([CH3:39])([CH3:38])[C:36]([OH:41])=[O:35])[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 90290tert-Butyl 2-bromo-2-methylpropionateHCID 66868277N-(3-(3-trifluoromethylphenyl)-4-hydroxybenzyl)-4-fluoro-N-methylbenzenesulfonamide

Product 1

HCID 668690412-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)-2-methylpropanoic acidYield 4.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-(3-(3-trifluoromethylphenyl)-4-hydroxybenzyl)-4-fluoro-N-methylbenzenesulfonamide (36) (50.0 mg, 0.114 mmol, 1 eq) in DMF (3 mL) under argon, was added t-butyl-2-bromo-2-methylpropanoate (66.0 mg, 0.296 mmol, 2.6 eq) and potassium carbonate (31 mg, 0.224 mmol, 2 eq). The mixture was stirred at 80° C. for 16 h, cooled to room temperature and partitioned with saturated sodium bicarbonate and EtOAc. The organic layer was separated, dried (Na2SO4), and concentrated in vacuo. The crude residue was dissolved in TFA/DCM (1 mL/1 mL) and stirred at room temperature for 1 h. Solvent was removed in vacuo and the residue was purified via reversed phase semi-preparative HPLC to afford 2.8 mg of 2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)-2-methylpropanoic acid (Example 34). 1HNMR (CD3OD, 400 MHz): δ 7.91 (m, 3H), 7.88 (m, 1H), 7.61 (m, 2H), 7.35 (t, 2H), 7.27 (d, 2H), 6.90 (d, 1H), 4.20 (s, 2H), 2.67 (s, 3H), 1.46 (s, 6H). MS (ESI): MH+=526.1. HPLC (Method B) tR=2.53 min.

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned with saturated sodium bicarbonate and EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude residue was dissolved in TFA/DCM (1 mL/1 mL)
  7. stirringstirred at room temperature for 1 h
  8. customSolvent was removed in vacuo
  9. customthe residue was purified via reversed phase semi-preparative HPLC

Sources & evidence

ORD record
ord-9e7332b10565418e9fad2ae0cb3142bc
Source dataset
uspto-grants-2014_09
Patent number
US08822467B2

Linked notes

Loading…