Ethanol → 2-(4-{2-[2-(4'-Formylbiphenyl-3-yl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methyl propionic acid ethyl ester

HRID 2228987Notes

Reaction equation

HRID 2228987 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[CH2:32](O)[CH3:33].[C:35]([O-:38])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([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)=CC=1>[CH2:1]([O:3][C:4](=[O:31])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:25]=[C:26]([C:33]4[CH:32]=[CH:11][C:10]([CH:35]=[O:38])=[CH:9][CH:14]=4)[CH:27]=[CH:28][CH:29]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2]

Participants

6

Reactant 3

HCID 702EthanolHCID 10340Sodium CarbonateHCID 120832362-(4-{2-[2-(3-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester

Product 1

HCID 865874062-(4-{2-[2-(4'-Formylbiphenyl-3-yl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methyl propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A solution of 2-(4-{2-[2-(3-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester (0.907 mmol) (see Ex. 3, part F) and 1-(4-formylphenyl)boronic acid (0.998 mmol) in toluene:ethanol (18.2 mL of a 1:1 solution) was treated with Na2CO3(aq) (0.906 mL of a 2M solution). A nitrogen atmosphere was applied, Pd(PPh3)4 (0.045 mmol) was added, and the orange mixture was heated at reflux for 2 h. After cooling to room temperature, the mixture was partitioned between ethyl acetate (20 mL) and H2O (30 mL). The layers were separated, and the aqueous phase was back-extracted with ethyl acetate (2×10 mL). Combined organic phases were washed with brine (20 mL), dried over Na2SO4, and concentrated. The product was purified by silica gel chromatography (20 g SiO2, 3:7 ethyl acetate:hexanes). Rf=0.24 in 1:4 ethyl acetate:hexanes; 1H NMR (400 MHz, CDCl3) δ10.03 (s, 1H), 9.21 (s, 1H), 9.02-8.94 (m, 3H), 8.81-8.78 (m, 2H), 8.46-8.41 (m, 1H), 8.36-8.30 (m, 1H), 6.79-6.71 (m, 4H), 4.23-4.16 (m, 4H), 2.94 (t, 2H), 2.37 (s, 3H), 1.26 (s, 6H), 1.24 (t, 3H); MS (EI) 514.2 (M+H)+.

Workup

  1. temperaturethe orange mixture was heated
  2. temperatureat reflux for 2 h
  3. customthe mixture was partitioned between ethyl acetate (20 mL) and H2O (30 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was back-extracted with ethyl acetate (2×10 mL)
  6. washCombined organic phases were washed with brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe product was purified by silica gel chromatography (20 g SiO2, 3:7 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-faf75b90a295413d9ade5888926304f4
Source dataset
uspto-grants-2002_07
Patent number
US06417212B1

Reaction notes

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