Cesium carbonate → HCID 86618561, compound

HRID 913149Notes

Reaction equation

HRID 913149 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([Cl:11])[CH:5]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:5]=[C:6]([Cl:11])[N:7]=[C:8]([NH:26][CH:23]2[CH2:22][CH2:21][N:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH2:25][CH2:24]2)[CH:9]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 93237Methyl 2,6-dichloroisonicotinateHCID 634876Binap, (A+-)-HCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 86618561HCID 86618561, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A stirred suspension of 2,6-dichloro-isonicotinic acid methyl ester (4.52 g, 21.9 mmol 1.0 equiv), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.39 g, 21.9 mmol, 1.0 equiv), palladium(II) acetate (0.50 g, 2.2 mmol, 0.1 equiv) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (1.39 g, 2.2 mmol, 0.1 equiv) in toluene (150 mL) was treated at rt with caesium carbonate (9.39 g, 28.5 mmol, 1.3 equiv) and then warmed to 80° C. After 6 h, the reaction mixture was poured into crashed ice and extracted twice with ethyl acetate. The combined organic layers were washed with brine and water, dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 5.40 g (67%) of the title compound as a light yellow solid. MS (ISP): 370.1 [M+H]+.

Workup

  1. additionthe reaction mixture was poured
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine and water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation under reduced pressure
  7. customThe crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-db3b26eb6d2a4862803552f88e35c7be
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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