4-Bromophenol → 4-(2-(4-Bromophenoxy)ethyl)morpholine

HRID 1054615Notes

Reaction equation

HRID 1054615 reaction equation
[N:1]1([CH2:7][CH2:8][OH:9])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Br:10][C:11]1[CH:16]=[CH:15][C:14](O)=[CH:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(OCC)(=O)C>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([O:9][CH2:8][CH2:7][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 78084-BromophenolHCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 20538154-(2-(4-Bromophenoxy)ethyl)morpholineYield 144.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 2-(morpholin-4-yl)ethanol (197 mg, 1.5 mmol) in THF (5 mL) was added 4-bromophenol (200 mg, 1.16 mmol), polymeric triphenylphosphine (0.5 g, 1.5 mmol) and DIAD (305 mg, 1.5 mmol). The mixture was degassed with nitrogen for 2 min and stirred at 110° C. for 17 hours. The cooled reaction mixture was filtered and the filtrate was concentrated in vacuo to give a residue, which was dissolved with ethyl acetate (50 mL), washed with 2 M aqueous NaOH (3×15 mL) and brine (2×20 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to give a residue, which was purified by flash chromatography on silica gel to give 4-[2-(4-bromophenoxy)ethyl]morpholine (480 mg, 100%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.35 (d, 2H), δ 6.70 (d, 2H), 4.07 (t, 2H), 3.74-3.71 (m, 4H), 2.78 (t, 2H), 2.57-2.55 (m, 4H).

Workup

  1. customThe mixture was degassed with nitrogen for 2 min
  2. customThe cooled reaction mixture
  3. filtrationwas filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customto give a residue, which
  6. washwashed with 2 M aqueous NaOH (3×15 mL) and brine (2×20 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a residue, which
  10. customwas purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-ffae91ce9ed94f8d9f01f6a3185e9313
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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