Potassium Fluoride → HCID 69872126, compound

HRID 2228994Notes

Reaction equation

HRID 2228994 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][C:27](Br)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[CH3:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O.[F-].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1>[CH2:1]([O:3][C:4](=[O:31])[C:5]([CH3:7])([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][C:27]([C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[CH3:32])=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)[CH3:6])[CH3:2]

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 27332672-Methylphenyl boronic acidHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 110273422-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester

Product 1

HCID 69872126HCID 69872126, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(4-{2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester (300 mg, 0.614 mmol) (see Ex. 2, part B), 2-methylphenylboronic acid (0.921 mmol), potassium fluoride (88.6 mg, 1.84 mmol), palladium acetate (1.3 mg, 0.14 μmol), and 2-(dicyclohexylphosphino)biphenyl (4.3 mg, 12.3 μmol) were combined under N2, to which anhydrous THF (1.23 mL) was added. The yellow mixture was heated at reflux for 12 h. After cooling to room temperature, the mixture was partitioned between Et2O (20 mL) and 1M NaOH (10 mL). The layers were separated, and the aqueous phase was back-extracted with Et2O (10 mL). Combined organic phases were dried over Na2SO4, and concentrated. The product was purified by silica gel chromatography (25 g SiO2, 1:4 ethyl acetate:hexanes) to yield the desired product as an oil. Rf=0.44 in 1:4 ethyl acetate:hexanes; 1H NMR (400 MHz, CDCl3) δ7.99 (d, J 8.6 Hz, 2H), 7.36 (d, J 8.6 Hz, 2H), 7.26-7.21 (m, 4H), 6.81-6.74 (m, 4H), 4.20 (t, J=6.6 Hz, 2H), 4.19 (q, J=7.2 Hz, 2H), 2.94 (t, J=6.6 Hz, 2H), 2.35 (s, 3H), 2.26 (s, 3H), 1.50 (s, 6H), 1.25 (t, J=7.2 Hz, 3H); MS (EI) 500.2 (M+H)−.

Workup

  1. additionwas added
  2. temperatureThe yellow mixture was heated
  3. temperatureat reflux for 12 h
  4. customthe mixture was partitioned between Et2O (20 mL) and 1M NaOH (10 mL)
  5. customThe layers were separated
  6. extractionthe aqueous phase was back-extracted with Et2O (10 mL)
  7. dry with materialCombined organic phases were dried over Na2SO4
  8. concentrationconcentrated
  9. customThe product was purified by silica gel chromatography (25 g SiO2, 1:4 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-9f13595ea1fb4189a49474c117d0719e
Source dataset
uspto-grants-2002_07
Patent number
US06417212B1

Reaction notes

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