Iodine → tert-Butyl (4-chloro-3-iodopyridin-2-yl)carbamate

HRID 1670247Notes

Reaction equation

HRID 1670247 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].CN(CCN(C)C)C.[Li]CCCC.[I:29]I.S([O-])(O)=O.[Na+]>C1COCC1.O>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[C:13]([I:29])=[C:12]([Cl:14])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 807IodineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 1516418tert-butyl N-(4-chloropyridin-2-yl)carbamateHCID 23665763Sodium BisulfiteHCID 178418339Butyllithium

Product 1

HCID 59852886tert-Butyl (4-chloro-3-iodopyridin-2-yl)carbamateYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

A solution of (4-chloro-pyridin-2-yl)-carbamic acid tert-butyl ester (CB Research and Development Inc., 5.0 g, 22.0 mmol), TMEDA (8 mL) in anhydrous THF (100 mL) was placed under a nitrogen atmosphere and cooled to −70° C. and treated dropwise with 2.5 M n-BuLi in hexanes (22.0 mL, 54.8 mmol) over a period of 30 min. The mixture was stirred at −70° C. for 1 h then treated dropwise with a solution of I2 (14 g, 110 mmol) in anhydrous THF (16 mL) at −70° C. After the addition was complete, the reaction was stirred at −70° C. for 30 min then allowed to warm to room temperature. The mixture was treated with a solution of sodium hydrogensulfite (16 g) in H2O (100 mL) and stirred for 30 min then extracted with EtOAc. The extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The product was purified by flash chromatography on SiO2 eluting with 0-5% MeOH/CH2Cl2 to give the title compound (5.8 g, 78%) as white solid. 1H NMR (DMSO-d6) δ 9.46 (s, 1H), 8.29 (d, 1H, J=5.6 Hz), 7.46 (d, 1H, J=5.0 Hz), 1.44 (s, 9H); MS (ESI−): m/z 352.99 (M−H)−.

Workup

  1. additionAfter the addition
  2. stirringthe reaction was stirred at −70° C. for 30 min
  3. temperatureto warm to room temperature
  4. stirringstirred for 30 min
  5. extractionthen extracted with EtOAc
  6. washThe extract was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe product was purified by flash chromatography on SiO2 eluting with 0-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-fdca7844b04045a5a08250f746871c9f
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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