Dimethylformamide → 2-chloro-5-(MethoxyMethoxy)pyridine

HRID 1498075Notes

Reaction equation

HRID 1498075 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[O:11]1[CH2:15]CC[CH2:12]1.CN(C)C=O.COCCl>O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:12][O:11][CH3:15])=[CH:8][N:9]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 7864Chloromethyl Methyl EtherHCID 8028TetrahydrofuranHCID 24758Sodium hydride2×HCID 8198212-Chloro-5-hydroxypyridine

Product 1

HCID 587641932-chloro-5-(MethoxyMethoxy)pyridineYield 94.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium hydride, 60% dispension in mineral oil (3:2, Sodium hydride:Mineral Oil, 2.32 g) was added portion wise to a solution of 6-Chloro-pyridin-3-ol (5.00 g, 38.6 mmol) in a mixture of Tetrahydrofuran (10.0 mL, 123 mmol) and N,N-Dimethylformamide (20.0 mL, 258 mmol). The mixture formed was stirred for 15 min and Chloromethyl Methyl Ether (3.66 mL, 48.2 mmol) was added dropwise. The above mixture was stirred for 6 hours (monitored by LCMS), poured into water and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried over MgSO4 and concentrated in vacuum. Purified on 40 g silica column eluting with 10-40% ethyl acetate in heptane to give 6.33 g of 2-chloro-5-(methoxymethoxy)pyridine.

Workup

  1. customThe mixture formed
  2. stirringThe above mixture was stirred for 6 hours (monitored by LCMS)
  3. extractionextracted with ethyl acetate
  4. washThe organic extracts were washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuum
  7. customPurified on 40 g silica column
  8. washeluting with 10-40% ethyl acetate in heptane

Sources & evidence

ORD record
ord-e6be05dc852a402a975ff834b2db2f9b
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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