Toluene → Morpholine

HRID 1443064Notes

Reaction equation

HRID 1443064 reaction equation
Br[C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[O:4][CH:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:6]1[O:11][CH2:10][CH2:9][NH:8][CH2:7]1.[C:22]1(C)C=CC=C[CH:23]=1>COCCO[AlH2-]OCCOC.[Na+]>[NH:8]1[CH2:9][CH2:10][O:11][CH2:6][CH2:7]1.[C:12]1([CH:5]([O:4][C:3]2[CH:18]=[CH:19][CH:20]=[CH:21][C:2]=2[CH:22]=[CH2:23])[CH:6]2[O:11][CH2:10][CH2:9][NH:8][CH2:7]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 2

HCID 1140Toluene2×HCID 11617199HCID 11617199, compound

Product 2

HCID 8083MorpholineHCID 68545195HCID 68545195, compound

Reagents, catalysts & solvents 1

HCID 16684438Red-AlSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of morpholinone 2 (0.255 g, 0.825 mmol) in toluene (10 mL), Red-Al (65% solution in toluene (0.8 mL, 2.55 mmol), was added dropwise at 0° C. over 20 min. The reaction mixture was stirred at 0-5° C. for 2.5 h. Excess Red-Al was destroyed by dropwise addition of 2 M NaOH solution (2.7 mL). The layers were separated and the aqueous layer was diluted with water (20 mL) and extracted with toluene (2×15 mL). The combined organic extract was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the product was purified on a column of silica gel using 10% methyl alcohol in ethyl acetate to give morpholine compound 3 (2-[Phenyl-(2-vinyl-phenoxy)-methyl]-morpholine) as a viscous colorless oil (0.154 g, 63%). 1H NMR (CDCl3) δ: 7.46-7.18 (m, 7H), 7.01 (m, 1H), 6.84 (t, 1H), 6.68 (d, 1H), 5.78 (dd, 1H), 5.29 (dd, 1H), 5.12 (d, 1H), 3.98-3.86 (m, 2H), 3.64 (dt, 1H), 2.86-2.72 (m, 2H), 2.66-2.54 (m, 2H); MS (ES) 296.1 [C19H21NO2+H]+; HPLC purity (94.3%); Analysis: Calcd. C19H21NO2.0.5H2O: C, 74.91; H, 7.23; N, 4.60. Found: C, 75.41; H, 7.09; N, 4.95.

Workup

  1. customExcess Red-Al was destroyed by dropwise addition of 2 M NaOH solution (2.7 mL)
  2. customThe layers were separated
  3. additionthe aqueous layer was diluted with water (20 mL)
  4. extractionextracted with toluene (2×15 mL)
  5. extractionThe combined organic extract
  6. washwas washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. customThe solvent was removed under reduced pressure
  9. customthe product was purified on a column of silica gel using 10% methyl alcohol in ethyl acetate

Sources & evidence

ORD record
ord-9841864363824dd6ad5a053cc12c4b4f
Source dataset
uspto-grants-2010_02
Patent number
US07659394B2

Reaction notes

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