Sulfuric Acid → [5-Hydroxy-2-methyl-4-(4'-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid

HRID 1063688Notes

Reaction equation

HRID 1063688 reaction equation
C[O:2][C:3]1[C:4]([S:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[CH:19][CH:18]=2)=[CH:5][C:6]([CH3:14])=[C:7]([CH:13]=1)[O:8][CH2:9][C:10]([OH:12])=[O:11].B(Br)(Br)Br.OS(O)(=O)=O>C(Cl)Cl.CO.CCOC(C)=O>[OH:2][C:3]1[C:4]([S:15][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=3)=[CH:21][CH:22]=2)=[CH:5][C:6]([CH3:14])=[C:7]([CH:13]=1)[O:8][CH2:9][C:10]([OH:12])=[O:11]

Participants

7

Reactant 3

HCID 1118Sulfuric AcidHCID 25134Boron tribromideHCID 9825600[5-Methoxy-2-methyl-4-(4'-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid

Product 1

HCID 22280112[5-Hydroxy-2-methyl-4-(4'-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of [5-Methoxy-2-methyl-4-(4′-trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-phenoxy]-acetic acid, prepared according to Example 4, (1.0 g, 2.2 mmol) in 75 mL DCM at 0° C., was treated with dropwise addition of BBr3 (5.5 mL of a 1.0 M solution in DCM). After 30 minutes, the reaction was carefully quenched with 50% NH4OH. The reaction was then acidified to pH 1 with conc. HCl, and extracted with EtOAC. The organic layer was dried (Na2SO4) and concentrated in vacuo. The crude reaction mixture was then taken up in MeOH, followed by addition of 50 μL H2SO4, and then refluxing for 3 hours. The reaction was then diluted with EtOAc, washed 1×50 mL water, dried (Na2SO4), and the reaction concentrated in vacuo. The resulting ester was purified by recrystallization from EtOAC/Hexanes. The ester was then saponified in the same manner as described for Example 1, to give the title compound in 37% overall yield. IR cm−1:3408, 1752, 1323; 400 MHz 1H NMR (DMSO-d6) δ 9.56 (s, 1H), 7.82 (d, 2H, J=8.4 Hz), 7.74 (d, 2H, J=8.4 Hz), 7.31 (d, 2H, J=8.4 Hz), 6.92 (s, 1H), 6.30 (s, 1H), 4.55 (s, 2H), 4.00 (s, 2H), 1.95 (s, 3H). Anal. Calc'd for C23H19F3NO4S.0.1 H2O C, 61.35; H, 4.30. found: C, 61.08; H, 3.92.

Workup

  1. customthe reaction was carefully quenched with 50% NH4OH
  2. extractionextracted with EtOAC
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude reaction mixture
  6. temperaturerefluxing for 3 hours
  7. washwashed 1×50 mL water
  8. dry with materialdried (Na2SO4)
  9. concentrationthe reaction concentrated in vacuo
  10. customThe resulting ester was purified by recrystallization from EtOAC/Hexanes

Sources & evidence

ORD record
ord-5485262703a44034af9c398443977a14
Source dataset
uspto-grants-2005_11
Patent number
US06964983B2

Reaction notes

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