Acetaldehyde → 1-{5-[Bis(methyloxy)methyl]-3-chloro-2-pyridinyl}ethanol

HRID 420748Notes

Reaction equation

HRID 420748 reaction equation
[CH3:1][O:2][CH:3]([O:12][CH3:13])[C:4]1[CH:5]=[C:6]([Cl:11])[C:7](I)=[N:8][CH:9]=1.C([Mg]Cl)(C)C.[CH:19](=[O:21])[CH3:20]>C1COCC1>[CH3:1][O:2][CH:3]([O:12][CH3:13])[C:4]1[CH:5]=[C:6]([Cl:11])[C:7]([CH:19]([OH:21])[CH3:20])=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 177Acetaldehyde2×HCID 580017105-[Bis(methyloxy)methyl]-3-chloro-2-iodopyridineHCID 178418918HCID 178418918, compound2×

Product 1

HCID 580017531-{5-[Bis(methyloxy)methyl]-3-chloro-2-pyridinyl}ethanolYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-[bis(methyloxy)methyl]-3-chloro-2-iodopyridine (239 mg, 0.762 mmol) in THF (1.5 ml) was slowly added to a solution of i-PrMgCl (400 μl, 0.800 mmol) in THF (1.5 ml) at −20° C. under N2 and the mixture was stirred at that temperature. After 30 min a small amount of starting material was still observed by LCMS. After 2 h, LCMS still showed some starting material. More i-PrMgCl (60 μl) was added and after 40 min disappearance of the starting material was observed by LCMS. Acetaldehyde (47 μl, 0.841 mmol) was added and the mixture stirred at −20° C. for 10 min. Partial conversion was observed by LCMS and no evolution was observed after 1 h. Excess acetaldehyde was added but no changes were observed after 30 min by LCMS. Then, it was quenched with saturated NH4Cl, extracted with EtOAc, dried (MgSO4), filtered, and concentrated to afford 177.4 mg of crude material as a brown oil. The mixture was purified by flash chromatography using Flashmaster II, a 10 g Merck silica gel cartridge, and mixtures of hexane and EtOAc as eluent. 1-{5-[bis(methyloxy)methyl]-3-chloro-2-pyridinyl}ethanol (67 mg, 38%) was isolated as a yellow oil.

Workup

  1. waitAfter 2 h
  2. stirringthe mixture stirred at −20° C. for 10 min
  3. waitno evolution was observed after 1 h
  4. waitno changes were observed after 30 min by LCMS
  5. customThen, it was quenched with saturated NH4Cl
  6. extractionextracted with EtOAc
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford 177.4 mg of crude material as a brown oil
  11. customThe mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-9c08729e4bbd47fd8d0d7a996bbcc628
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

Loading…