Morpholine → 4-(4-Bromo-3-fluorobenzyl)morpholine

HRID 1924017Notes

Reaction equation

HRID 1924017 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[F:10].[NH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].[OH-].[K+]>ClC(Cl)C.ClCCl.O>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:4][C:3]=1[F:10]

Participants

9

Reactant 5

HCID 8083MorpholineHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 27834114-Bromo-3-fluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 534178184-(4-Bromo-3-fluorobenzyl)morpholineYield 70.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

4-Bromo-3-fluorobenzaldehyde (4.69 g, 23.10 mmol) was dissolved in degassed dichloroethane (40 mL) and stirred under nitrogen. Morpholine (2.015 mL, 23.10 mmol) was added followed by sodium triacetoxyborohydride (6.37 g, 30.03 mmol) portionwise. The reaction was stirred over night. Saturated NaHCO3 (aq) was added. The phases were separated and the organic phase was washed with 2M HCl (aq). A solid precipitated in the separation funnel. The solid was isolated by filtration. The water phase and the solid were combined and dichloromethane was added. The pH was adjusted to ca 10 by adding solid KOH. The water phase was extracted with dichloromethane (2×) and the organic phase was dried and concentrated to give 4-(4-bromo-3-fluorobenzyl)morpholine (4.45 g, 70%) as a solid.

Workup

  1. stirringThe reaction was stirred over night
  2. customThe phases were separated
  3. washthe organic phase was washed with 2M HCl (aq)
  4. customA solid precipitated in the separation funnel
  5. customThe solid was isolated by filtration
  6. extractionThe water phase was extracted with dichloromethane (2×)
  7. customthe organic phase was dried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-19a6db1e9e2c4125a9356428876ea19f
Source dataset
uspto-grants-2012_05
Patent number
US08178529B2

Reaction notes

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