Dimethylformamide → 3-Bromo-5-(ethoxymethyl)pyridine

HRID 1818132Notes

Reaction equation

HRID 1818132 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].I[CH2:21][CH3:22].CN(C=O)C>C1COCC1.[Cl-].[Na+].O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][OH:9])[CH:5]=[N:6][CH:7]=1.[Br:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH2:8][O:9][CH2:21][CH3:22])[CH:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 6340IodoethaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 2784733(5-Bromo-3-pyridinyl)methanol

Product 2

HCID 2784733(5-Bromo-3-pyridinyl)methanolHCID 219843463-Bromo-5-(ethoxymethyl)pyridineYield 120.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

(5-Bromopyridin-3-yl)methanol was prepared according to the published procedure (Zhang, N. et al, J. Med. Chem., 45, 2832-2840 (2002)). A solution of (5-bromopyridin-3-yl)methanol (7.39 g, 39.3 mmol) in THF was cooled to 0° C. Sodium bis(trimethylsilyl)amide (39.3 mL of a 1.0 M solution in THF) was added, and the reaction was stirred for 20 minutes. Iodoethane (3.46 mL, 43.2 mmol) and DMF were added, and the reaction was allowed to warm to ambient temperature and stirred overnight. Brine was added, and the aqueous layer was extracted twice with hexanes. The combined organic fractions were concentrated under reduced pressure, and the residue was purified by HPFC (eluting with hexanes:ethyl acetate in a gradient from 100:0 to 70:30) to provide 5.11 g of 3-bromo-5-ethoxymethylpyridine as a colorless oil.

Workup

  1. stirringstirred overnight
  2. extractionthe aqueous layer was extracted twice with hexanes
  3. concentrationThe combined organic fractions were concentrated under reduced pressure
  4. customthe residue was purified by HPFC (
  5. washeluting with hexanes

Sources & evidence

ORD record
ord-0b14be0ace8f4a1faac7b40f4000475e
Source dataset
uspto-grants-2009_10
Patent number
US07598382B2

Reaction notes

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