Dimethyl Sulfoxide → Tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

HRID 1895756Notes

Reaction equation

HRID 1895756 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[CH:3]=1.CS(O[CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)(=O)=O.CS(C)=O.C(=O)([O-])[O-].[K+].[K+]>CCCCCC.CCOC(C)=O.O>[O:8]=[C:4]1[CH:3]=[C:2]([O:1][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH:7]=[CH:6][NH:5]1

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineHCID 546960044-Hydroxy-2(1H)-pyridinone

Product 1

HCID 67366878Tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateYield 17%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-hydroxypyridin-2(1H)-one (11.11 g, 100 mmol) and tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (27.9 g, 100 mmol) in a 100 mL round bottom flask was applied vacuum 5 minutes, vented to nitrogen, added DMSO (100 mL), and then added potassium carbonate (13.20 g, 220 mmol). Placed in a 90° C. oil bath under nitrogen for 4.5 hours. The reaction mixture was added to 1000 mL water and 1000 mL EtOAc, then washed EtOAc with additional water (4×500 mL), dried with MgSO4, filtered and concentrated to 27.3 g oily white solids. This material was slurried 200 mL refluxing EtOAc, allowed to cool to rt, filtered, and washed with 2×50 mL EtOAc then 2×50 mL of hexane to give product (4.86 g, 16.5 mmol, 17%) as a white crystalline powder. MS (ESI) 239.1 (M+1-56, indicating loss of t-butyl group the Boc group in the MS).

Workup

  1. customvacuum 5 minutes
  2. customPlaced in a 90° C.
  3. customfor 4.5 hours
  4. dry with materialwashed EtOAc with additional water (4×500 mL), dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to 27.3 g oily white solids
  7. temperaturerefluxing EtOAc
  8. filtrationfiltered
  9. washwashed with 2×50 mL EtOAc

Sources & evidence

ORD record
ord-180b71c9d1ee4fa597d35e04f09fbed0
Source dataset
uspto-grants-2013_08
Patent number
US08513424B2

Reaction notes

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