Potassium Carbonate → HCID 45107506, compound

HRID 386538Notes

Reaction equation

HRID 386538 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 CarbonateHCID 67072607HCID 67072607, compoundHCID 90426408HCID 90426408, compound

Product 1

HCID 45107506HCID 45107506, compoundYield 52.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (125 mg, 0.471 mmol), trans-tert-butyl 2-methyl-4-(methylsulfonyloxy)piperidine-1-carboxylate (138.2 mg, 0.471 mmol, Example 1) and potassium carbonate (163 mg, 1.178 mmol) in DMF (4.0 mL) was heated at 110° C. for 20 hrs. The reaction mixture was cooled to room temperature and diluted with EtOAc and water. The aqueous layer was extracted further with EtOAc (3×). 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 in hexane) to yield cis isomer of tert-butyl 2-methyl-4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (114.6 mg, 52% yield) as an off-white solid. 1H NMR (500 MHz, CDCl3). δ 8.07 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.24 (d, J=7.70 Hz, 1H), 6.06 (dd, J=7.70, 2.75 Hz, 1H), 5.95 (d, J=2.20 Hz, 1H), 4.64-4.70 (m, 1H), 4.35-4.45 (m, 1H), 3.91-3.98 (m, 1H), 3.18-3.28 (m, 1H), 3.09 (s, 9H), 1.95-2.04 (m, 2H), 1.89-1.96 (m, 1H), 1.75-1.84 (m, 1H), 1.48 (s, 9H), 1.27 (d, J=7.15 Hz, 3H). MS (ESI) 463 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous layer was extracted further with EtOAc (3×)
  3. washThe combined organic layers were washed with brine/water (1:1, 2×)
  4. dry with materialdried (Na2SO4)
  5. customevaporated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (0-100% EtOAc in hexane)

Sources & evidence

ORD record
ord-175fc7de3c1a47878bca4139666dc40d
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

Loading…