Hydrochloric Acid → 5-[Bis(methyloxy)methyl]-3-chloro-2-iodopyridine

HRID 420747Notes

Reaction equation

HRID 420747 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](C=O)[CH:5]=[N:6][C:7]=1[I:8].[CH:11](OC)([O:14][CH3:15])[O:12][CH3:13].Cl.C(Cl)Cl>CO>[CH3:13][O:12][CH:11]([O:14][CH3:15])[C:4]1[CH:3]=[C:2]([Cl:1])[C:7]([I:8])=[N:6][CH:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 9005Trimethyl orthoformateHCID 580017995-Chloro-6-iodo-3-pyridinecarbaldehyde

Product 1

HCID 580017105-[Bis(methyloxy)methyl]-3-chloro-2-iodopyridineYield 79%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 5-chloro-6-iodo-3-pyridinecarbaldehyde (260 mg, 0.972 mmol), trimethyl orthoformate (1.064 ml, 9.72 mmol), HCl (3M in MeOH) (0.778 ml, 2.333 mmol), DCM (1.5 ml) and MeOH (1.5 ml) was stirred at 50° C. for 3 h. TLC showed full conversion. The solution was cooled to room temperature and concentrated under vacuum. The residue was diluted with sat. NaHCO3 and EtOAc. Extraction, drying (MgSO4), filtration, and concentration afforded 271.5 mg of crude material. Purification by flash chromatography using Flashmaster II, a 5 g silica gel cartridge, and mixtures of hexane and EtOAc as eluent afforded 5-[bis(methyloxy)methyl]-3-chloro-2-iodopyridine (239.9 mg, 79%) as a yellow oil. It will be used in the next step without further purification.

Workup

  1. temperatureThe solution was cooled to room temperature
  2. concentrationconcentrated under vacuum
  3. additionThe residue was diluted with sat. NaHCO3 and EtOAc
  4. extractionExtraction
  5. customdrying
  6. filtration(MgSO4), filtration, and concentration
  7. customafforded 271.5 mg of crude material
  8. customPurification by flash chromatography

Sources & evidence

ORD record
ord-60a42d9d8ff04684825170c3bcd4af0a
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

Loading…