Morpholine → 4-((6-Bromopyridin-2-yl)methyl)morpholine

HRID 385759Notes

Reaction equation

HRID 385759 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([CH:8]=O)[CH:5]=[CH:4][CH:3]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(OCC)(=O)C.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 8083MorpholineHCID 27570096-Bromopyridine-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 234381474-((6-Bromopyridin-2-yl)methyl)morpholine

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Reductive Amination Method A: A solution of 6-bromopyridine-2-carbaldehyde (3 g, 16.13 mmol) and morpholine (1.41 mL, 16.13 mmol) in 1,2-dichloroethane (22 mL) under argon was charged with sodium triacetoxyborohydride (4.79 g, 22.58 mmol) and allowed to stir for 14 hours. The reaction mixture was then diluted with ethyl acetate (100 mL), saturated aqueous sodium bicarbonate (60 mL), and saturated aqueous sodium carbonate (90 mL). The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate (2×50 mL) and brine (2×50 mL), dried over sodium sulfate, filtered, and concentrated. The resulting material was purified by silica gel chromatography (30-100% ethyl acetate/hexanes) to afford the title compound as a white solid.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with saturated aqueous sodium bicarbonate (2×50 mL) and brine (2×50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting material was purified by silica gel chromatography (30-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7a2993e79121460786f310c5dcd6413a
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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