Lithium Hydroxide → [4-(4-Methoxy-4''-trifluoromethoxy-[1,1';3',1'']terphenyl-5'-ylmethoxy)-2-methyl-phenoxy]-acetic acid

HRID 19503

Reaction equation

HRID 19503 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25]C)=[C:20]([CH3:27])[CH:19]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[CH:7]=1.[F:28][C:29]([F:41])([F:40])[O:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.[C:42](=[O:45])([O-])[O-:43].[K+].[K+].[OH-].[Li+]>O1CCOCC1.C1(P([Pd](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)C.O>[CH3:15][O:14][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[CH:5]=[C:4]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:42]([OH:43])=[O:45])=[C:20]([CH3:27])[CH:19]=3)[CH:3]=[C:2]([C:34]3[CH:35]=[CH:36][C:31]([O:30][C:29]([F:41])([F:40])[F:28])=[CH:32][CH:33]=3)[CH:7]=2)=[CH:13][CH:12]=1

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 691074205-Bromo-3-(4-ethoxy-3-methyl-phenoxymethyl)-4'-methoxy-biphenyl

Product 1

HCID 11599107[4-(4-Methoxy-4''-trifluoromethoxy-[1,1';3',1'']terphenyl-5'-ylmethoxy)-2-methyl-phenoxy]-acetic acid

Reagents, catalysts & solvents 4

HCID 178420554HCID 178420554, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

5-Bromo-3-(4-ethoxy-3-methyl-phenoxymethyl)-4′-methoxy-biphenyl 15 (50 mg, 0.11 mmol) and 4-trifluoromethoxyphenylboronic acid (30 mg, 0.15 mmol, 1.3 equiv.) are dissolved in dioxane (0.5 mL). Potassium carbonate (38 mg, 0.27 mmol), water (0.05 mL) and ethanol (0.05 mL) are added, followed by tetrakis (triphenylphosphino)palladium (15.6 mg, 0.13 mmol). The mixture is stirred under nitrogen and subjected to microwave (170° C. for 10 min). Cooling, addition of 0.25 mL of aqueous 1N lithium hydroxide solution, and stirring for 3 hours at room temperature, followed by reversed-phase purification yielded [4-(4-methoxy-4″-trifluoromethoxy-[1,1′;3′,1″]terphenyl-5′-ylmethoxy)-2-methyl-phenoxy]-acetic acid A2. 1H-NMR (400 MHz, CDCl3) δ=7.50 (m, 3H), 7.42 (m, 4H), 7.17 (d, J=8.0 Hz, 2H), 6.87 (d, J=8.0 Hz, 2H), 6.75 (d, J=2.8 Hz, 1H), 6.65 (dd, J=8.8, 2.8 Hz, 1H), 6.58 (d, J=8.8 Hz, 1H), 5.17 (s, 2H), 4.50 (s, 2H), 3.73 (s, 3H), 2.16 (s, 3H). 19F-NMR (376 MHz, CDCl3) δ=−57.8. MS calculated for C30H26F3O6 (M+H+) 539.17. found 539.0.

Workup

  1. custom(170° C. for 10 min)
  2. temperatureCooling
  3. stirringstirring for 3 hours at room temperature
  4. customfollowed by reversed-phase purification

Sources & evidence

ORD record
ord-23ddb7be655f4c35a298c86d3c047f61
Source dataset
uspto-grants-2010_06
Patent number
US07745445B2

Linked notes

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