Ethylene Glycol → HCID 66658303, compound

HRID 1881725Notes

Reaction equation

HRID 1881725 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[Cl:12][C:13]1[CH:14]=[C:15]([CH:20]=[O:21])[CH:16]=[N:17][C:18]=1[CH3:19].[CH2:22](O)[CH2:23][OH:24].C1(C)C=CC=CC=1>O>[Cl:12][C:13]1[C:18]([CH3:19])=[N:17][CH:16]=[C:15]([CH:20]2[O:24][CH2:23][CH2:22][O:21]2)[CH:14]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 580017625-chloro-6-methyl-3-Pyridinecarboxaldehyde

Product 1

HCID 66658303HCID 66658303, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

p-Toluenesulfonic acid (5.53 mg, 0.032 mmol) was added to a mixture of 5-chloro-6-methyl-3-pyridinecarbaldehyde (for a synthesis see WO20006/137485 A1 Example 256) (250 mg, 1.607 mmol), ethylene glycol (179 μl, 3.21 mmol), and toluene (8 ml) and the mixture was heated under reflux as water was azeotropically removed (Dean-Stark). The progression was monitored by TLC (50% hexane:EtOAc) and HPLC. More ethylene glycol (180 μl) and TsOH (3 mg) were added and after 46 hr full conversion was observed by HPLC. 10% Na2CO3 and EtOAc were added. Extraction, drying (MgSO4), and filtration afforded 3-chloro-5-(1,3-dioxolan-2-yl)-2-methylpyridine (274.3 mg, 86%) pure enough to be used in the next step.

Workup

  1. temperaturethe mixture was heated
  2. customwas azeotropically removed (Dean-Stark)
  3. additionMore ethylene glycol (180 μl) and TsOH (3 mg) were added and after 46 hr full conversion
  4. addition10% Na2CO3 and EtOAc were added
  5. extractionExtraction
  6. customdrying
  7. filtration(MgSO4), and filtration

Sources & evidence

ORD record
ord-cdbaa35d6dab4c3d9b655f8e1b3c4f26
Source dataset
uspto-grants-2012_11
Patent number
US08318940B2

Reaction notes

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