Potassium Carbonate → Methyl 5-{2-[(tert-butoxycarbonyl)amino]ethoxy}-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylate

HRID 577584Notes

Reaction equation

HRID 577584 reaction equation
[OH:1][C:2]1[C:3]([C:13]([O:15][CH3:16])=[O:14])=[C:4]([CH3:12])[C:5]([O:8][CH:9]([CH3:11])[CH3:10])=[N:6][CH:7]=1.Br[CH2:18][CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24].C([O-])([O-])=O.[K+].[K+]>CC#N>[C:23]([O:22][C:21]([NH:20][CH2:19][CH2:18][O:1][C:2]1[C:3]([C:13]([O:15][CH3:16])=[O:14])=[C:4]([CH3:12])[C:5]([O:8][CH:9]([CH3:10])[CH3:11])=[N:6][CH:7]=1)=[O:27])([CH3:26])([CH3:25])[CH3:24]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 86723810Methyl 5-hydroxy-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylate

Product 1

HCID 86723811Methyl 5-{2-[(tert-butoxycarbonyl)amino]ethoxy}-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl 5-hydroxy-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylate (131c, 0.70 g, 3.1 mmol), tert-butyl (2-bromoethyl)carbamate (0.76 g, 3.4 mmol) and K2CO3 (0.86 g, 6.2 mmol) in CH3CN (24 mL) was degassed with N2 and refluxed for 15 hours. To the reaction mixture was added brine (40 mL) and EtOAc (40 mL). The aqueous layer was extracted with EtOAc (20 mL). The combined organic layers were washed with brine (60 mL), dried over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 10/1) to give methyl 5-{2-[(tert-butoxycarbonyl)amino]ethoxy}-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylate (131d, 0.74 g, 65%) as yellow oil.

Workup

  1. customwas degassed with N2
  2. temperaturerefluxed for 15 hours
  3. additionTo the reaction mixture was added brine (40 mL) and EtOAc (40 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  5. washThe combined organic layers were washed with brine (60 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by column chromatography (petroleum ether/EtOAc, 10/1)

Sources & evidence

ORD record
ord-a462c22429b34adab6de7e2b26087a33
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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