tert-Butanol → HCID 59363634, compound

HRID 1094770Notes

Reaction equation

HRID 1094770 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5](C(O)=O)=[CH:4][CH:3]=1.CC[N:17]([CH:21](C)C)C(C)C.P(N=[N+]=[N-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=[O:25].[CH3:43][C:44]([OH:47])([CH3:46])[CH3:45]>C1(C)C=CC=CC=1.CCOCC>[CH3:43][C:44]([O:47][C:21]([NH:17][C:5]1[C:6]([C:8]([O:10][CH3:11])=[O:9])=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=1)=[O:25])([CH3:46])[CH3:45]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 123414Diphenylphosphoryl azideHCID 15679401HCID 15679401, compound

Product 1

HCID 59363634HCID 59363634, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

6-methyl-2-[(methyloxy)carbonyl]-3-pyridinecarboxylic acid D33 (1.15 g) was suspended in toluene (40 ml) and DIPEA (1.25 ml, 7.16 mmol) was added, causing the complete dissolution of the solid. This mixture was stirred 10 minutes at room temperature, then diphenyl azidophosphate (1.35 ml, 6.26 mmol) was added in one portion and the mixture was stirred at reflux for 1 hour. The solution was cooled at room temperature and t-BuOH (2.5 ml, 26 mmol) was added in one portion. The mixture was then stirred at 70° C. for 1 hour and then cooled at room temperature, Et2O (50 ml) was added and the resulting solution washed with NaHCO3 saturated solution. The water phases were joined together and back-extracted with Et2O. The two organic solutions were joined together, dried over Na2SO4 and evaporated at reduced pressure, obtaining the crude target material as pale yellow oil. This material was purified by flash chromatography on silica gel (Biotage, EtOAc/Cy from 10/90 to 70/30; Snap-100 g column). The title compound D34 (1.315 g) was obtained as white solid. UPLC (Basic GEN_QC): rt=0.68 minutes, peak observed: 267 (M+1). C13H18N2O4 requires 266. 1H NMR (400 MHz, CDCl3) δ ppm 10.13 (bs., 1 H), 8.77 (d, 1 H), 7.34 (d, 1 H), 4.03 (s, 3H), 2.59 (s, 3 H), 1.53-1.56 (m, 9 H).

Workup

  1. dissolutionthe complete dissolution of the solid
  2. stirringthe mixture was stirred
  3. temperatureat reflux for 1 hour
  4. temperatureThe solution was cooled at room temperature
  5. stirringThe mixture was then stirred at 70° C. for 1 hour
  6. temperaturecooled at room temperature
  7. washthe resulting solution washed with NaHCO3 saturated solution
  8. extractionback-extracted with Et2O
  9. dry with materialdried over Na2SO4
  10. customevaporated at reduced pressure
  11. customobtaining the crude target material as pale yellow oil
  12. customThis material was purified by flash chromatography on silica gel (Biotage, EtOAc/Cy from 10/90 to 70/30; Snap-100 g column)

Sources & evidence

ORD record
ord-5da378fc96414c5aae4b196a0beb73b9
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

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