Acetic Acid → 2,5-Dimethyl-4-[[2-methyl-4-[(4-trifluoromethyl-phenylamino)methyl]phenyl]sulfanyl]-phenoxy-acetic acid ethyl ester

HRID 985058Notes

Reaction equation

HRID 985058 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([S:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]=O)=[CH:17][C:16]=2[CH3:23])=[CH:9][C:8]=1[CH3:24])[CH3:2].[F:26][C:27]([F:36])([F:35])[C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([S:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][NH:32][C:31]3[CH:33]=[CH:34][C:28]([C:27]([F:26])([F:35])[F:36])=[CH:29][CH:30]=3)=[CH:17][C:16]=2[CH3:23])=[CH:9][C:8]=1[CH3:24])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 99644-(Trifluoromethyl)anilineHCID 5049666Sodium triacetoxyborohydrideHCID 207681204-[(4-Formyl-2-methylphenyl)sulfanyl]-2,5-dimethylphenoxy-acetic acid ethyl ester

Product 1

HCID 207681062,5-Dimethyl-4-[[2-methyl-4-[(4-trifluoromethyl-phenylamino)methyl]phenyl]sulfanyl]-phenoxy-acetic acid ethyl esterYield 98.5%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred solution of compound 21.4 (13.5 g, 37.7 mmol) in CHCl3 (135 mL) was successively added 4-(trifluoromethyl)aniline (6.07 g, 37.7 mmol) and AcOH (3.24 mL). After stirring at room temperature for 30 min, the reaction was cooled to 0° C., sodium triacetoxyborohydride (12.0 g, 56.6 mmol) was added, and the reaction was stirred at room temperature for 3 h. The reaction mixture was poured into 150 mL of ice-water and the product was extracted with 2×50 mL CHCl3. The organics were sequentially washed with 150 mL aqueous NaHCO3 and 150 mL brine, dried over MgSO4, and concentrated to a yellow oil, which was purified with flash chromatography (SiO2 gel 60 N, eluted with 10% EtOAc/hexanes—20% EtOAc/hexanes). The fractions containing the desired product were combined and concentrated to yield a colorless solid (18.7 g). 1H NMR (400 MHz) (CDCl3) δ 7.38 (2H, d, J=8.5 Hz); 7.20 (1H, s); 7.14 (1H, s); 6.97 (1H, d, J=8.1 Hz); 6.70-6.50 (4H, m); 4.66 (2H, s); 4.40-4.20 (5H, m); 2.38 (3H, s); 2.30 (3H, s); 2.22 (3H, s); 1.31 (3H, t, J=7.1 Hz).

Workup

  1. temperaturethe reaction was cooled to 0° C.
  2. stirringthe reaction was stirred at room temperature for 3 h
  3. extractionthe product was extracted with 2×50 mL CHCl3
  4. washThe organics were sequentially washed with 150 mL aqueous NaHCO3 and 150 mL brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to a yellow oil, which
  7. customwas purified with flash chromatography (SiO2 gel 60 N, eluted with 10% EtOAc/hexanes—20% EtOAc/hexanes)
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-de75d65717ee421995dd5ebbb1abb4c0
Source dataset
uspto-grants-2005_03
Patent number
US06869975B2

Reaction notes

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