Chloromethyl Methyl Ether → 2-Fluoro-5-(1-methoxymethoxy-ethyl)-pyridine

HRID 1640877Notes

Reaction equation

HRID 1640877 reaction equation
C(N(C(C)C)CC)(C)C.Cl[CH2:11][O:12][CH3:13].[F:14][C:15]1[N:20]=[CH:19][C:18]([CH:21]([OH:23])[CH3:22])=[CH:17][CH:16]=1>C(Cl)Cl.C(Cl)(Cl)Cl.C(O)(C)C>[F:14][C:15]1[CH:16]=[CH:17][C:18]([CH:21]([O:23][CH2:11][O:12][CH3:13])[CH3:22])=[CH:19][N:20]=1

Participants

6

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 666001661-(6-Fluoropyridin-3-yl)ethan-1-ol

Product 1

HCID 667382922-Fluoro-5-(1-methoxymethoxy-ethyl)-pyridineYield 66%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
0 °C

Procedure

Add diisopropylethylamine and chloromethoxymethane to a solution of 1-(6-fluoro-pyridin-3-yl)-ethanol (3.0 g, 21.3 mmol) in DCM at 0° C. Continue to stir the mixture for 30 min at 0° C., then overnight at RT. Dilute the mixture with chloroform/IPA (3/1). Wash the solution with saturated aqueous sodium chloride. Dry it over sodium sulfate. Concentrate the solution in vacuo to a dark residue. Purify by column chromatography (hexane→20% ethyl acetate in hexane) to afford the title compound as a colorless solid (3 g, 66%). MS (ES) m/z 186 [M+1]+.

Workup

  1. customovernight
  2. customat RT
  3. washWash the solution with saturated aqueous sodium chloride
  4. dry with materialDry it over sodium sulfate
  5. concentrationConcentrate the solution in vacuo to a dark residue
  6. customPurify by column chromatography (hexane→20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-5c8e96397a38481eb7404ae9fadd1166
Source dataset
uspto-grants-2012_02
Patent number
US08114872B2

Reaction notes

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