Iodine → tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

HRID 1969174Notes

Reaction equation

HRID 1969174 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][CH:3]=1.[Li]CCCC.[I:21]I.O>C1COCC1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[C:4]([I:21])[CH:3]=1

Participants

6

Reactant 4

HCID 807IodineHCID 962WaterHCID 7330593(6-Chloro-pyridin-3-yl)-carbamic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 53415320tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamateYield 32.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To the solution of tert-butyl (6-chloropyridin-3-yl)carbamate (160 g, 0.7 mol) in 1 L of anhydrous THF was added n-BuLi (600 mL, 1.5 mol) at −78° C. under N2 atmosphere. After the addition was finished, the solution was stirred at −78° C. for 30 min, and the solution of I2 (177.68 g, 0.7 mol) in 800 mL of anhydrous THF was added. Then the solution was stirred at −78° C. for 4 hrs. TLC indicated the reaction was over. Water was added for quench, and EtOAc was added to extract twice. The combined organic phases were washed with brine, dried over Na2SO4, filtered and purified by flash chromatography to afford 80 g of tert-butyl (6-chloro-4-iodopyridin-3-yl)carbamate as a yellow solid (32.3%).

Workup

  1. additionAfter the addition
  2. stirringThen the solution was stirred at −78° C. for 4 hrs
  3. customfor quench
  4. additionEtOAc was added
  5. extractionto extract twice
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. custompurified by flash chromatography

Sources & evidence

ORD record
ord-5bf221f0b879467d8382c230603cb966
Source dataset
uspto-grants-2013_04
Patent number
US08426450B1

Reaction notes

Loading…