Potassium Phosphate, Tribasic → HCID 118062400, 화합물

HRID 631921노트

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HRID 631921 반응식
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]

참가 물질

9

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

생성물 1

HCID 118062400HCID 118062400, 화합물수율 61.4%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
105 °C

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-3f9846cc50d047c49937021937931def
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321738B2

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