Potassium Phosphate, Tribasic → methyl 4'-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-ethyl]amino]-3-(cyclohexyloxy)-4-biphenylcarboxylate

HRID 2078656ノート

反応式

HRID 2078656 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:28])[CH2:9][N:10]([CH2:18][CH2:19][NH:20][C:21]2[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=2)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[CH:6][CH:7]=1.[CH:29]1([O:35][C:36]2[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][C:41]=2[C:42]([O:44][CH3:45])=[O:43])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C1(NC2CCCCC2)CCCCC1.C1(NC2CCCCC2)CCCCC1.C([O-])(=O)C>[C:13]([O:12][C:11]([N:10]([CH2:9][C@@H:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[OH:28])[CH2:18][CH2:19][NH:20][C:21]1[CH:26]=[CH:25][C:24]([C:38]2[CH:39]=[CH:40][C:41]([C:42]([O:44][CH3:45])=[O:43])=[C:36]([O:35][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)[CH:37]=2)=[CH:23][CH:22]=1)=[O:17])([CH3:16])([CH3:15])[CH3:14]

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 24822808(3-(Cyclohexyloxy)-4-(methoxycarbonyl)phenyl)boronic acid2 回HCID 67098101HCID 67098101、化合物

生成物 1

HCID 67097299methyl 4'-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-ethyl]amino]-3-(cyclohexyloxy)-4-biphenylcarboxylate収率 53.9%

試薬・触媒・溶媒 3

HCID 11851071bis(dicyclohexylamine)-palladium(II) acetate触媒HCID 702Ethanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

To a solution of tert-butyl [(2R)-2-(3-chlorophenyl)-2-hydroxyethyl][2-[(4-iodophenyl)amino]ethyl]carbamate (200 mg), [3-(cyclohexyloxy)-4-(methoxycarbonyl)phenyl]-boronic acid (193 mg), potassium phosphate (246 mg) in ethanol (1.5 ml) was added bis(dicyclohexylamine) -palladium(II) acetate (32.9 mg) and the mixture was stirred at 60° C. for 3 hours under nitrogen atmosphere. After warming to 80° C., the mixture was stirred at the same temperature for 3 hours. To the reaction mixture were added [3-(cyclohexyloxy)-4-(methoxycarbonyl)phenyl]boronic acid (107 mg) and bis(dicyclohexylamine)palladium(II) acetate (10.9 mg) and the mixture was stirred at 80° C. for 3 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered through the celite cake. The filtrate was washed with water and brine and dried over magnesium sulfate. Filtration followed by evaporation under reduced pressure gave the crude product which was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/6 to 1/2) to give methyl 4′-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-ethyl]amino]-3-(cyclohexyloxy)-4-biphenylcarboxylate (130 mg) as a white solid.

後処理

  1. temperatureAfter warming to 80° C.
  2. stirringthe mixture was stirred at the same temperature for 3 hours
  3. stirringthe mixture was stirred at 80° C. for 3 hours
  4. temperatureAfter cooling to room temperature
  5. filtrationfiltered through the celite cake
  6. washThe filtrate was washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationFiltration
  9. customfollowed by evaporation under reduced pressure
  10. customgave the crude product which
  11. customwas purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/6 to 1/2)

出典と根拠

ORDレコード
ord-d2734bfdc4564585a7662799e54a7e95
出典データセット
uspto-grants-2011_04
特許番号
US07928264B2

反応ノート

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