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

HRID 561007

Reaction equation

HRID 561007 reaction equation
CCN(C(C)C)C(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>ClCCl.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 N,N′-diisopropylethylamine and chloromethoxymethane to a solution of 1-(6-fluoro-pyridin-3-yl)-ethanol (3.0 g, 21.3 mmol) in dichloromethane at 0° C. Continue to stir the mixture for 30 min at 0° C., then overnight at room temperature. Dilute the mixture with chloroform/isopropyl alcohol (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 product as a colorless solid (3 g, 66%). MS (ES) m/z 186 [M+1]+.

Workup

  1. customovernight
  2. customat room temperature
  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-fab50c36c9d14844a11c4da0c5f58bf0
Source dataset
uspto-grants-2011_11
Patent number
US08063212B2

Linked notes

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