Hydrochloric Acid → 2-(4-Morpholinophenyl)ethanol

HRID 272698Notes

Reaction equation

HRID 272698 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][OH:10])=[CH:4][CH:3]=1.[NH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl.C([O-])(O)=O.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:11]1([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][OH:10])=[CH:4][CH:3]=2)[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 728512-(4-Bromophenyl)ethanolHCID 516892Sodium BicarbonateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 135928032-(4-Morpholinophenyl)ethanolYield 50.2%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A mixture of 2-(4-bromophenyl)ethanol (0.70 mL, 5 mmol), morpholine (0.52 mL, 6 mmol), LHMDS (11 mL, IM solution in THF), Pd2 (dba)3 (46 mg, 0.05 mmol), and CyMAP (24 mg, 0.06 mmol) was heated to reflux for 16 hours. Cooled to room temperature. Acidified with IM HCl, stirred for 10 minutes, and neutralized with saturated NaHCO3. Partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 520 mg (50%) of the desired product. MS (ESI) m/e 208 (M+H)+, 1H NMR (300 MHz, CDCl3): □ 7.15 (d, J=8.48 Hz, 2H), 6.88 (d, J=8.48 Hz, 2H), 3.78-3.87 (m, 6H), 3.11-3.14 (m, 4H), 2.79 (t, J=6.61 Hz, 2H), 1.43 (m, 1H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours
  3. customPartitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-13264c7218f849018dea5700b0206018
Source dataset
uspto-grants-2008_11
Patent number
US07456169B2

Reaction notes

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