Potassium Carbonate → HCID 45107506, compound

HRID 386537Notes

Reaction equation

HRID 386537 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[C:4](=[O:18])[CH:3]=1.[CH3:19][C@H:20]1[CH2:25][C@@H:24](OS(C)(=O)=O)[CH2:23][CH2:22][N:21]1[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[CH3:19][CH:20]1[CH2:25][CH:24]([O:1][C:2]2[CH:7]=[CH:6][N:5]([C:8]3[CH:9]=[CH:10][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][CH:13]=3)[C:4](=[O:18])[CH:3]=2)[CH2:23][CH2:22][N:21]1[C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32]

Participants

7

Reactant 3

HCID 11430Potassium Carbonate2×HCID 67072607HCID 67072607, compoundHCID 118086349HCID 118086349, compound

Product 1

HCID 45107506HCID 45107506, compoundYield 10.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridine-2(1H)-one (173 mg, 0.652 mmol), cis-tert-butyl 2-methyl-4-(methylsulfonyloxy)piperidine-1-carboxylate (191 mg, 0.652 mmol) and potassium carbonate (180 mg, 1.304 mmol) in DMF (3.0 mL) was heated at 140° C. for 6 hrs and 100° C. overnight. To the above mixture additional potassium carbonate (90 mg, 1 equiv.) was added and the reaction was heated at 120° C. for 3 hrs and then cooled to room temperature. The mixture was diluted with EtOAc and water and the aqueous layer was extracted further with EtOAc (4×). The combined organic layers were washed with brine/water (1:1, 2×), dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexane) to yield trans-isomer of tert-butyl 2-methyl-4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (31.4 mg, 10.4%) as an off-white solid. 1H NMR (500 MHz, CDCl3). δ 8.07 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.25 Hz, 2H), 7.22 (d, J=7.70 Hz, 1H), 6.02 (dd, J=7.70, 2.20 Hz, 1H), 5.97 (d, J=2.20 Hz, 1H), 4.50-4.66 (m, 2H), 4.09-4.13 (m, 1H), 3.09 (s, 3H), 2.91-3.05 (m, 1H), 2.10-2.22 (m, 1H), 1.96-2.07 (m, 1H), 1.69-1.85 (m, 1H), 1.51-1.64 (m, 1H), 1.48 (s, 9H), 1.23 (d, J=7.15 Hz, 3H). MS (ESI) 463 (M+H).

Workup

  1. temperaturethe reaction was heated at 120° C. for 3 hrs
  2. temperaturecooled to room temperature
  3. extractionthe aqueous layer was extracted further with EtOAc (4×)
  4. washThe combined organic layers were washed with brine/water (1:1, 2×)
  5. dry with materialdried (Na2SO4)
  6. customevaporated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (0-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-36aee96fb1de46fc892079d4ea001121
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

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