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

HRID 2078656Notes

Reaction equation

HRID 2078656 reaction equation
[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]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 24822808(3-(Cyclohexyloxy)-4-(methoxycarbonyl)phenyl)boronic acid2×HCID 67098101HCID 67098101, compound

Product 1

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

Reagents, catalysts & solvents 3

HCID 11851071bis(dicyclohexylamine)-palladium(II) acetateCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-d2734bfdc4564585a7662799e54a7e95
Source dataset
uspto-grants-2011_04
Patent number
US07928264B2

Reaction notes

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