Potassium Fluoride → HCID 69872472, compound

HRID 2417048Notes

Reaction equation

HRID 2417048 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].[F: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]([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[F:32])=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2]

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343542-Fluorophenylboronic acidHCID 110273422-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester

Product 1

HCID 69872472HCID 69872472, 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-fluorophenylboronic 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=0.48 in 1:4 ethyl acetate:hexanes; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J=8.0 Hz, 2H), 7.60 (d, J=8 Hz, 2H), 7.47-7.42 (m, 1H), 7.34-7.28 (m, 1H), 7.22-7.11 (m, 2H), 6.81-6.73 (m, 4H), 4.20 (q, J=6.8 Hz, 2H), 4.17 (t, J=6.6 Hz, 2H), 2.94 (t, J=.6.6 Hz, 2H), 2.35 (s, 3H), 1.50 (s, 6H), 1.24 (t, J=6.8 Hz, 3H); MS (EI) 504.2 (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-81073c9949a048d6838b40dafe6072a8
Source dataset
uspto-grants-2004_11
Patent number
US06825222B2

Reaction notes

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