Potassium Fluoride → 2-(4-{2-[2-(2',6'-Dichloro-biphenyl-4-yl)-5-methyloxazol-4-yl]-ethoxy}-phenoxy)-2-methylpropionic acid ethyl ester

HRID 398127ノート

反応式

HRID 398127 の反応式
[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].[Cl:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[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[C:33]([Cl:32])=[CH:38][CH:37]=[CH:36][C:35]=4[Cl:39])=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2]

参加物

7

反応物 4

HCID 522689Potassium FluorideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343322,6-Dichlorobenzeneboronic acidHCID 110273422-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester

生成物 1

HCID 698701212-(4-{2-[2-(2',6'-Dichloro-biphenyl-4-yl)-5-methyloxazol-4-yl]-ethoxy}-phenoxy)-2-methylpropionic acid ethyl ester

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒

実験手順

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), 2,6-dichlorophenylboronic 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=0.50 in 1:4 ethyl acetate:hexanes; MS (EI) 554.2 (M+H)+.

後処理

  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)

出典と根拠

ORDレコード
ord-11660e3984ca469dad3f1a35150342ff
出典データセット
uspto-grants-2003_08
特許番号
US06610696B2

反応ノート

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