Sodium Carbonate → 3-{4-[1-(2-Biphenyl-4-yl-4-isopropyl-oxazol-5-yl)-ethoxy]-2-methyl-phenyl}-propionic Acid

HRID 860677Notes

Reaction equation

HRID 860677 reaction equation
C[O:2][C:3](=[O:31])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([C:15]2[O:19][C:18]([C:20]3[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=3)=[N:17][C:16]=2[CH:27]([CH3:29])[CH3:28])[CH3:14])=[CH:8][C:7]=1[CH3:30].[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:23]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:24]=[CH:25][C:20]([C:18]2[O:19][C:15]([CH:13]([O:12][C:9]3[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([OH:2])=[O:31])=[C:7]([CH3:30])[CH:8]=3)[CH3:14])=[C:16]([CH:27]([CH3:29])[CH3:28])[N:17]=2)=[CH:21][CH:22]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 101521383-(4-{1-[2-(4-Bromo-phenyl)-4-isopropyl-oxazol-5-yl]-ethoxy}-2-methyl-phenyl)-propionic acid methyl ester

Product 1

HCID 101278343-{4-[1-(2-Biphenyl-4-yl-4-isopropyl-oxazol-5-yl)-ethoxy]-2-methyl-phenyl}-propionic Acid

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 3-(4-{1-[2-(4-bromo-phenyl)-4-isopropyl-oxazol-5-yl]-ethoxy}-2-methyl-phenyl)-propionic acid methyl ester (150 mg, 0.308 mmol) in toluene (4 ml) and THF (0.5 ml) is bubbled with nitrogen for 10 minutes. To this solution is added phenyl boronic acid (56 mg, 0.46 mmol), Pd(OAc)2 (10 mg), and sodium carbonate (1.0 ml, 2.0 N). The suspension is heated to 85° C. for 8 hours and the mixture is then extracted with EtOAc (3×10 mL). The combined organics are dried over Na2SO4 and concentrated, purified by silica gel chromatography (Hexanes/EtOAc, 7.5/2.5) to afford the biphenyl intermediate as a colorless oil. The ester is then dissolved in MeOH (1.0 ml) and THF (0.5 ml) and treated with NaOH (2.0 N, 1.5 ml). The mixture is stirred at room temperature for 2 hours and concentrated to an aqueous residue. It is then neutralized with 5 N HCl to pH˜4 and extracted with EtOAc (3×5 ml). The combined organics are dried over Na2SO4 and concentrated, purified by silica gel chromatography (Hexanes/EtOAc, 5/5, then Hexanes/EtOAc/HOAc 5/5/0.02) to afford the acid as a colorless oil (35 mg, 24%). MS (ES): 470.1 (M++1).

Workup

  1. extractionthe mixture is then extracted with EtOAc (3×10 mL)
  2. dry with materialThe combined organics are dried over Na2SO4
  3. concentrationconcentrated
  4. custompurified by silica gel chromatography (Hexanes/EtOAc, 7.5/2.5)

Sources & evidence

ORD record
ord-aec894e05f2742b0ab4ec233ac3aa3e6
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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