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

HRID 705500Notes

Reaction equation

HRID 705500 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.C([O-])([O-])=O.[K+].[K+].CS(C)=O>O.C(Cl)Cl.CO>[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 45%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A 250 mL round bottom flask was charged with 4-hydroxypyridin-2(1H)-one (6.13 g, 55.1 mmol), tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (12.83 g, 45.9 mmol) (prepared according to the procedure described in patent application WO-2009/012275), K2CO3 (14.60 g, 106 mmol) and DMSO (56 mL). The mixture was heated to 100° C. for 3 hours and then allowed to cool to room temperature overnight. The resulting mixture was diluted with H2O (300 mL) and extracted with EtOAc (2×150 mL). The organic layers were combined and concentrated in vacuo to a white solid. The solid was purified by flash chromatography (SiO2, 0-100% EtOAc in CH2Cl2 and then SiO2, 0-10% MeOH in CH2Cl2) to yield tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (6.05 g, 45% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 12.34 (br. s., 1H) 7.21 (d, J=7.28 Hz, 1H) 5.96 (dd, J=7.28, 2.51 Hz, 1H) 5.87 (d, J=2.26 Hz, 1H) 4.35-4.58 (m, 1H) 3.59-3.80 (m, 2H) 3.17-3.41 (m, 2H) 1.87-2.08 (m, 2H) 1.65-1.87 (m, 2H) 1.47 (s, 9H). MS (ESI) 295 (M+H).

Workup

  1. customprepared
  2. temperatureto cool to room temperature overnight
  3. extractionextracted with EtOAc (2×150 mL)
  4. concentrationconcentrated in vacuo to a white solid
  5. customThe solid was purified by flash chromatography (SiO2, 0-100% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-4938e9108d3d4baea32592c35a28ecac
Source dataset
uspto-grants-2015_11
Patent number
US09174965B2

Reaction notes

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