Carbon Dioxide → 5-tert-Butoxycarbonylamino-2-chloroisonicotinic acid

HRID 2224328Notes

Reaction equation

HRID 2224328 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].CN(CCN(C)C)C.[Li]CCCC.[C:29](=[O:31])=[O:30]>CCOCC>[C:1]([O:5][C:6]([NH:7][C:8]1[C:13]([C:29]([OH:31])=[O:30])=[CH:12][C:11]([Cl:14])=[N:10][CH:9]=1)=[O:15])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 7330593(6-Chloro-pyridin-3-yl)-carbamic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 105641445-tert-Butoxycarbonylamino-2-chloroisonicotinic acidYield 35%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of (6-chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (3.28 g, 14.3 mmol) and TMEDA (6.7 mL, 44.4 mmol) in Et2O (100 mL) at −78° C. was treated with n-BuLi (4.3 mL, 10 M, 43 mmol). After stirring the mixture at −78° C. for 2 hours CO2 was bubbled into the reaction and the solution was warmed to 0° C. Water was added and the mixture was extracted with EtOAc. The aqueous layer was acidified and extracted with Et2O. The Et2O layer was washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The residual solid was triturated with Hexane/Et2O to give 25A (1.38 g, 35%) HPLC Rt=2.98 min.

Workup

  1. customwas bubbled into the reaction
  2. additionWater was added
  3. extractionthe mixture was extracted with EtOAc
  4. extractionextracted with Et2O
  5. washThe Et2O layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent was removed in vacuo
  8. customThe residual solid was triturated with Hexane/Et2O

Sources & evidence

ORD record
ord-226e41213aa748c1ab9fdb13c32b6644
Source dataset
uspto-grants-2008_05
Patent number
US07378426B2

Reaction notes

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