Benzyl Bromide → 2-(4-Benzyloxy-3-bromophenyl)-4-propylmorpholine

HRID 2102351Notes

Reaction equation

HRID 2102351 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([CH2:14][CH2:15][CH3:16])[CH2:9]2)[CH:5]=[CH:4][C:3]=1[OH:17].C(=O)([O-])[O-].[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[CH2:24]([O:17][C:3]1[CH:4]=[CH:5][C:6]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([CH2:14][CH2:15][CH3:16])[CH2:9]2)=[CH:7][C:2]=1[Br:1])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 574406772-Bromo-4-(4-propylmorpholin-2-yl)phenol

Product 1

HCID 574406932-(4-Benzyloxy-3-bromophenyl)-4-propylmorpholineYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To the phenol from example 30 (117.5 mg, 0.39 mmol) in dry DMF (10 ml), under an atmosphere of nitrogen, was added potassium carbonate (75 mg, 0.54 mmol) and benzyl bromide (0.07 ml, 0.54 mmol). The reaction mixture was heated to 150° C. for 48 hours. After cooing, the reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate (50 ml) and water (50 ml). The aqueous layer was then re-extracted with ethyl acetate (2×20 ml). The combined organic extracts were then dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give the crude product as a brown oil. This was purified by column chromatography on silica eluting with dichloromethane:methanol (98:2) to give the title compound as a colourless oil (153 mg, 0.39 mmol, 100%). 1H NMR (CDCl3, 400 MHz) δ: 0.93 (t, 3H), 1.56 (q, 2H), 2.05 (t, 1H), 2.25 (t, 1H), 2.37 (t, 2H), 2.82 (d, 1H), 2.92 (d, 1H), 3.85 (t, 1H), 4.02 (d, 1H), 4.52 (d, 1H), 5.15 (s, 2H), 6.87 (d, 1H), 7.20 (d, 1H), 7.30 (d, 1H), 7.37 (t, 2H), 7.45 (d, 2H), 7.58 (s, 1H). LRMS: m/z 392 (M-H+).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between ethyl acetate (50 ml) and water (50 ml)
  3. extractionThe aqueous layer was then re-extracted with ethyl acetate (2×20 ml)
  4. dry with materialThe combined organic extracts were then dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude product as a brown oil
  8. customThis was purified by column chromatography on silica eluting with dichloromethane:methanol (98:2)

Sources & evidence

ORD record
ord-b6afb4b314e0402c8784d0a9279143d2
Source dataset
uspto-grants-2009_08
Patent number
US07576081B2

Reaction notes

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