Iodine → 1,1-Dimethylethyl N-[4-iodo-6-(1-methylethoxy)-3-pyridinyl]carbamate

HRID 400581Notes

Reaction equation

HRID 400581 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[N:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[I:24]I.[Cl-].[NH4+]>C(OCC)C.C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([I:24])=[CH:11][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[N:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 807IodineHCID 25517Ammonium ChlorideHCID 69571751HCID 69571751, compoundHCID 178418339Butyllithium

Product 1

HCID 600268161,1-Dimethylethyl N-[4-iodo-6-(1-methylethoxy)-3-pyridinyl]carbamateYield 63%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 13.7 g of 5-[(tert-butoxycarbonyl)amino]-2-(isopropoxy)pyridine (54.3 mmol) and 18.1 mL of N,N,N′-tetramethylethylenediamine (120 mmol) in 200 mL of anhydrous diethyl ether was cooled to −78° C. and treated with n-BuLi (2.5 M in hexanes, 48 mL, 120 mmol) under an inert atmosphere. The mixture was placed in a −8° C. bath for 1 hour and allowed to slowly warm to room temperature. After 40 minutes, the flask was cooled to −8° C. and stirred for 4 hours. The mixture was then cooled to −78° C., treated with a solution of iodine (19.0 g, 75 mmol) in 100 mL of anhydrous THF, and the resulting mixture was stirred for 16 hours while allowing the bath to warm to 11° C. The reaction mixture was poured into a rapidly stirring aqueous saturated ammonium chloride solution (200 mL) and diluted with 100 mL of water and 300 mL of diethyl ether. The phases were separated and the aqueous layer was extracted with 200 mL of diethyl ether. The combined organic layers were washed with two 200 mL portions of sodium thiosulfate (10% aqueous solution), dried over sodium sulfate, decanted, and concentrated in vacuo. Chromatography on SiO2 (10% to 50% ethyl acetate in hexanes, gradient) gave the title product as an oil, which solidified on standing (13 g, 63% yield).

Workup

  1. customwas placed in a −8° C.
  2. customfor 1 hour
  3. temperaturethe flask was cooled to −8° C.
  4. temperatureThe mixture was then cooled to −78° C.
  5. stirringthe resulting mixture was stirred for 16 hours
  6. temperatureto warm to 11° C
  7. customThe phases were separated
  8. extractionthe aqueous layer was extracted with 200 mL of diethyl ether
  9. washThe combined organic layers were washed with two 200 mL portions of sodium thiosulfate (10% aqueous solution)
  10. dry with materialdried over sodium sulfate
  11. customdecanted
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a3bfbb6673cc46a6848575a7372a1b26
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

Loading…