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

HRID 2078656노트

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HRID 2078656 반응식
[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]

참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 24822808(3-(Cyclohexyloxy)-4-(methoxycarbonyl)phenyl)boronic acid2회HCID 67098101HCID 67098101, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 11851071bis(dicyclohexylamine)-palladium(II) acetate촉매HCID 702Ethanol용매HCID 8857Ethyl Acetate용매

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온도
60 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-d2734bfdc4564585a7662799e54a7e95
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07928264B2

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