Acetate → 4-Benzyl-2,2-dimethylmorpholine

HRID 601561Notes

Reaction equation

HRID 601561 reaction equation
[CH2:1]([N:8]([CH2:12][C:13]([CH3:15])=[CH2:14])[CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[OH-].[Na+].[BH4-].[Na+]>O.C1COCC1.[Hg]>[CH2:1]([N:8]1[CH2:9][CH2:10][O:11][C:13]([CH3:15])([CH3:14])[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 175AcetateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 574215002-[Benzyl(2-methylprop-2-EN-1-YL)amino]ethan-1-OL

Product 1

HCID 155791114-Benzyl-2,2-dimethylmorpholineYield 54%

Reagents, catalysts & solvents 3

HCID 23931MercuryCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add 2-[benzyl-(2-methyl-allyl)-amino]-ethanol (13.0 g, 63.2 mmol) to a slurry of mercury (It) acetate (20.7 g, 65.0 mmol) in water (45 mL) and THF (45 mL). After 3 h, treat the mixture with NaOH (25 mL, 2.5 M aqueous, 125 mmol) followed by NaBH4 (2.72 g, 71.9 mmol). After 19 h, decant the mixture away from the metallic mercury and add to a separatory funnel with tert-butyl methyl ether (250 mL). Separate the organic solution, wash with water (250 mL), filter through a silica plug, and concentrate. Purify the residue by flash chromatography using a gradient from 5% to 10% tert-butyl methyl ether in CH2Cl2. Collect and concentrate the fractions containing product then dissolve the residue in hexanes (100 mL). Filter the solution through Celite® to remove metallic mercury and then concentrate the filtrate to give the title compound (7.01 g, 54%) as a colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.20-7.40 (5H, m), 3.60 (2H, m), 3.42 (2H, s), 2.29 (2H, m), 2.10 (2H, s), 1.14 (6H, s).

Workup

  1. waitAfter 19 h
  2. customdecant the mixture away from the metallic mercury
  3. additionadd to a separatory funnel with tert-butyl methyl ether (250 mL)
  4. customSeparate the organic solution
  5. washwash with water (250 mL)
  6. filtrationfilter through a silica plug
  7. concentrationconcentrate
  8. customPurify the residue by flash chromatography
  9. customCollect
  10. concentrationconcentrate the fractions
  11. additioncontaining product
  12. dissolutionthen dissolve the residue in hexanes (100 mL)
  13. filtrationFilter the solution through Celite®
  14. customto remove metallic mercury
  15. concentrationconcentrate the filtrate

Sources & evidence

ORD record
ord-37c08aa48852434494165117eb9d1adc
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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