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

HRID 9382

Reaction equation

HRID 9382 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-db1f569af9f74fb396843cd058260599
Source dataset
uspto-grants-2006_08
Patent number
US07091214B2

Linked notes

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