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

HRID 1016635Notes

Reaction equation

HRID 1016635 reaction equation
C([Li])CCC.[Cl:6][C:7]1[N:12]=[CH:11][C:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:9][CH:8]=1.CN(C)CCN(C)C.[I:29]I.[Cl-].[NH4+]>CCOCC>[Cl:6][C:7]1[N:12]=[CH:11][C:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[C:9]([I:29])[CH:8]=1

Participants

7

Reactant 5

HCID 807IodineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 7330593(6-Chloro-pyridin-3-yl)-carbamic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 53415320tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamateYield 55.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-10 °C

Procedure

n-Butyllithium (1.6M in hexanes, 22 mL, 35 mmol) was added dropwise to a stirred, cooled (−78° C.) solution of 1,1-dimethylethyl (6-chloro-3-pyridinyl)carbamate (Description 6, 2.68 g, 11.7 mmol) and N,N,N′,N′-tetramethylethylenediamine (5.3 mL, 4.1 g, 35 mmol) in ether (60 mL). The mixture was allowed to warm to −10° C. and stirred for 2 h. The mixture was cooled to −78° C. and a cooled (−10° C.) solution of iodine (6.0 g, 24 mmol) in ether (20 mL) was added dropwise. The mixture was allowed to warm to room temperature and stirred for 18 h. Saturated aqueous ammonium chloride was added and the mixture was extracted with ether. The combined organic fractions were washed with aqueous sodium metabisulfite (10%), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with hexane and the solid was collected and dried in vacuo to give the title compound as a brown solid (2.3 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.94 (1H, s), 7.73 (1H, s), 6.64 (1H, br s), and 1.54 (9H, s).

Workup

  1. temperatureThe mixture was cooled to −78° C.
  2. additionwas added dropwise
  3. temperatureto warm to room temperature
  4. stirringstirred for 18 h
  5. extractionthe mixture was extracted with ether
  6. washThe combined organic fractions were washed with aqueous sodium metabisulfite (10%)
  7. dry with materialdried (MgSO4)
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was triturated with hexane
  10. customthe solid was collected
  11. customdried in vacuo

Sources & evidence

ORD record
ord-98ade5f867bc469288969a6a14a2a87f
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

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