Methanol → 2-(4-Benzyloxy-3-bromophenyl)-4-propylmorpholine

HRID 600231Notes

Reaction equation

HRID 600231 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.CO>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

6

Reactant 4

HCID 887MethanolHCID 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 cooling, 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 (9832) 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. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue partitioned between ethyl acetate (50 ml) and water (50 ml)
  4. extractionThe aqueous layer was then re-extracted with ethyl acetate (2×20 ml)
  5. dry with materialThe combined organic extracts were then dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product as a brown oil
  9. customThis was purified by column chromatography on silica eluting with dichloromethane

Sources & evidence

ORD record
ord-781c087d90b94352adaf5fce8281ac6d
Source dataset
uspto-grants-2011_03
Patent number
US07902188B2

Reaction notes

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