Cesium carbonate → Methyl cis(+/-)-4-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)pyridine-2-carboxylate

HRID 43752

Reaction equation

HRID 43752 reaction equation
Cl.[CH3:2][O:3][C@H:4]1[C@@H:9]([NH:10][C:11](=[O:20])[O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8][CH2:7][NH:6][CH2:5]1.Cl[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([C:28]([O:30][CH3:31])=[O:29])[CH:23]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH2:13]([O:12][C:11]([NH:10][C@H:9]1[CH2:8][CH2:7][N:6]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([C:28]([O:30][CH3:31])=[O:29])[CH:23]=2)[CH2:5][C@H:4]1[O:3][CH3:2])=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 820890Methyl 4-ChloropicolinateHCID 86648698Benzyl cis(+/-)-[3-methoxypiperidin-4-yl]carbamate hydrochloride

Product 1

HCID 86648699Methyl cis(+/-)-4-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)pyridine-2-carboxylateYield 32.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

Benzyl cis(±)-[3-methoxypiperidin-4-yl]carbamate hydrochloride obtained in Example (160a) (192.83 mg, 0.64 mmol) and methyl 4-chloropyridine-2-carboxylate (100 mg, 0.58 mmol) were dissolved in dioxane (3 ml) and DMF (1 mL). Palladium acetate (26.17 mg, 0.12 mmol), BINAP (145.16 mg, 0.23 mmol) and cesium carbonate (569.68 mg, 1.75 mmol) were added, and the mixture was stirred using a microwave irradiation reactor at 160° C. for 40 minutes. Water was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Thereafter, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=40/1, 20/1, 10/1) to obtain 74.8 mg of the title compound as a yellow oily substance.

Workup

  1. customa microwave irradiation reactor at 160° C. for 40 minutes
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThen, the organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThereafter, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=40/1, 20/1, 10/1)

Sources & evidence

ORD record
ord-f635cac799ac48cfaad64c6aa0fa050d
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Linked notes

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