Sodium hydride → 4-[2-[(5-Bromo-3-pyridyl)methoxy]ethyl]morpholine

HRID 712685Notes

Reaction equation

HRID 712685 reaction equation
[H-].[Na+].[N:3]1([CH2:9][CH2:10][OH:11])[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[Br:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH2:19]Cl)[CH:18]=1>CN(C=O)C>[Br:12][C:13]1[CH:18]=[C:17]([CH2:19][O:11][CH2:10][CH2:9][N:3]2[CH2:8][CH2:7][O:6][CH2:5][CH2:4]2)[CH:16]=[N:15][CH:14]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 611632-MorpholinoethanolHCID 117012593-Bromo-5-(chloromethyl)pyridine

Product 1

HCID 1176673744-[2-[(5-Bromo-3-pyridyl)methoxy]ethyl]morpholineYield 50.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To the NaH (484 mg, 60% in mineral oil, 12.1 mmol) in DMF (dry, 1 mL) at 0° C., is slowly added 2-morpholin-4-yl-ethanol (1.47 ml, 12.1 mmol). Then the mixture is stirred at 0° C. for 30 min. 3-bromo-5-chloromethyl-pyridine (500 mg, 2.42 mmol) is added at 0° C. The mixture is then stirred at room temperature overnight and is quenched by adding water dropwise. The mixture is partitioned between DCM and water. The DCM phase is separated and then washed with water twice. The DCM phase is evaporated under high vacuum. The residue is separated by silica gel flash column (MeOH/DCM 0 to 5% gradient, then 5%) to obtain 370 mg of 4-[2-[(5-bromo-3-pyridyl)methoxy]ethyl]morpholine.

Workup

  1. customat 0° C.
  2. stirringThe mixture is then stirred at room temperature overnight
  3. customis quenched
  4. additionby adding water dropwise
  5. customThe mixture is partitioned between DCM and water
  6. customThe DCM phase is separated
  7. washwashed with water twice
  8. customThe DCM phase is evaporated under high vacuum
  9. customThe residue is separated by silica gel flash column (MeOH/DCM 0 to 5% gradient

Sources & evidence

ORD record
ord-319c449d003d4337ac383494e5e2478c
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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