Water → Tert-butyl (6-chloro-4-iodopyridin-3-yl)(methyl)carbamate

HRID 1969175Notes

Reaction equation

HRID 1969175 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])=[C:4]([I:16])[CH:3]=1.[H-].[Na+].[CH3:19]I.O>C1COCC1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:19])[C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[C:4]([I:16])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 53415320tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

Product 1

HCID 57443399Tert-butyl (6-chloro-4-iodopyridin-3-yl)(methyl)carbamateYield 99.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To the solution of tert-butyl (6-chloro-4-iodopyridin-3-yl)carbamate (61 g, 0.172 mol) in 300 mL of anhydrous THF was added 60% NaH (7.6 g, 0.189 mol) at 0° C. under N2 atmosphere. After the addition was finished, the solution was stirred for 30 min, and then the solution of MeI (26.92 g, 0.189 mol) in 100 mL of dry THF was added. Then the solution was stirred at 0° C. for 3 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 concentrated to afford 63 g of crude tert-butyl (6-chloro-4-iodopyridin-3-yl)(methyl)carbamate used into the following de-protection without the further purification.

Workup

  1. additionAfter the addition
  2. stirringThen the solution was stirred at 0° C. for 3 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. concentrationconcentrated

Sources & evidence

ORD record
ord-15b000c8b7be4d4ca220ae1843198ca8
Source dataset
uspto-grants-2013_04
Patent number
US08426450B1

Reaction notes

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