Sodium Bicarbonate → [4'-[3-Methyl-4-[[[((R)-1-phenylethyl)oxy]carbonyl]amino]isoxazol-5-yl]biphenyl-4-yl]acetic acid ethyl ester

HRID 553712ノート

反応式

HRID 553712 の反応式
[C:1]1([C@H:7]([O:9][C:10](=[O:25])[NH:11][C:12]2[C:13]([CH3:24])=[N:14][O:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:26]([O:28][C:29](=[O:46])[CH2:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=1)[CH3:27].C(=O)(O)[O-].[Na+]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].COCCOC>[CH2:26]([O:28][C:29](=[O:46])[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:20]2[CH:21]=[CH:22][C:17]([C:16]3[O:15][N:14]=[C:13]([CH3:24])[C:12]=3[NH:11][C:10]([O:9][C@@H:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH3:8])=[O:25])=[CH:18][CH:19]=2)=[CH:33][CH:32]=1)[CH3:27]

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 46737998Ethyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetateHCID 66660383(1R)-1-Phenylethyl N-(5-(4-bromophenyl)-3-methyl-4-isoxazolyl)carbamate

生成物 1

HCID 67352169[4'-[3-Methyl-4-[[[((R)-1-phenylethyl)oxy]carbonyl]amino]isoxazol-5-yl]biphenyl-4-yl]acetic acid ethyl ester

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

[5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester (39 g, 97.2 mmol), [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (31 g, 107 mmol), and sodium bicarbonate (32.6 g, 389 mmol) were combined in 3:1 DME:H2O (500 mL), and the mixture was purged with N2 for 15 minutes. (1,1′-Bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (2.13 g, 2.91 mmol) was added, and the reaction was purged with N2 for an additional 10 minutes and then stirred at 90° C. overnight. The mixture was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with H2O, dried over MgSO4, filtered, and concentrated, and the residue was purified by silica gel chromatography (EtOAc/hexane gradient) to give the title compound.

後処理

  1. customH2O (500 mL), and the mixture was purged with N2 for 15 minutes
  2. customthe reaction was purged with N2 for an additional 10 minutes
  3. customThe mixture was partitioned between EtOAc and H2O
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined organic layers were washed with H2O
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue was purified by silica gel chromatography (EtOAc/hexane gradient)

出典と根拠

ORDレコード
ord-ef9395f576574672bca26cf195d16bd4
出典データセット
uspto-grants-2011_11
特許番号
US08048902B2

反応ノート

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