Potassium Phosphate, Tribasic → HCID 118062400, compound

HRID 631921Notes

Reaction equation

HRID 631921 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][N:11]([CH3:25])[C:12]=2[NH:13][C:14](=[O:24])[O:15][C@@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH3:17])=[CH:4][CH:3]=1.[CH2:26]([O:28][C:29]([C:31]1([C:36]2[CH:41]=[CH:40][CH:39]=[C:38](B3OC(C)(C)C(C)(C)O3)[CH:37]=2)[CH2:33][CH:32]1CC)=[O:30])[CH3:27].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH2:26]([O:28][C:29]([C:31]1([C:36]2[CH:37]=[C:38]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[N:9]=[N:10][N:11]([CH3:25])[C:12]=4[NH:13][C:14]([O:15][C@@H:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH3:17])=[O:24])=[CH:4][CH:3]=3)[CH:39]=[CH:40][CH:41]=2)[CH2:32][CH2:33]1)=[O:30])[CH3:27]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 71266457HCID 71266457, compoundHCID 131735430Ethyl 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 118062400HCID 118062400, compoundYield 61.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

To a mixture of (R)-1-phenylethyl 4-(4-bromophenyl)-1-methyl-1H-1,2,3-triazol-5-ylcarbamate (120 mg, 0.3 mmol), ethyl 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylic acid ethyl ester (142 mg, 0.449 mmol), palladium(II) acetate (10.1 mg, 0.05 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (36.8 mg, 0.1 mmol), and potassium phosphate tribasic (190 mg, 0.9 mmol) in a vial were added toluene (2.25 mL) and water (0.5 mL) at room temperature under nitrogen atmosphere. The resulting light brown suspension was disconnected from the nitrogen line and the reaction mixture was heated to 105° C. and the progress of the reaction was followed by TLC analysis and it was completed after 1 h at this temperature. Then, it was cooled to room temperature and diluted with water and ethyl acetate. The two layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layer was washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the crude compound which was purified using an ISCO (40 g) column chromatography eluting with 0-70% ethyl acetate in hexanes. The desired fractions were combined and the solvent was removed under vacuum to obtain (R)-1-(4′-(1-methyl-5-((1-phenylethoxy)-carbonylamino)-1H-1,2,3-triazol-4-yl)biphenyl-3-yl)cyclopropanecarboxylic acid ethyl ester as a white solid (94 mg, 61% yield). LC/MS calcd. for C30H30N4O4 (m/e) 510.0, obsd. 511.1 (M+H, ES+).

Workup

  1. temperatureThen, it was cooled to room temperature
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
  4. washThe combined organic layer was washed with brine solution
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationFiltration and concentration
  7. customgave the crude compound which
  8. customwas purified
  9. washeluting with 0-70% ethyl acetate in hexanes
  10. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-3f9846cc50d047c49937021937931def
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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