Dichloromethane → 4-Ethyl-2-(4-nitrophenyl)morpholine

HRID 1261968Notes

Reaction equation

HRID 1261968 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:4].C(Cl)Cl.[CH2:17]([NH:19][CH2:20][CH2:21]O)[CH3:18].C(N(CC)C(C)C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>>[CH2:17]([N:19]1[CH2:20][CH2:21][O:4][CH:3]([C:5]2[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=2)[CH2:2]1)[CH3:18]

Participants

7

Reactant 6

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 80722-(Ethylamino)ethanolHCID 12052TriethylsilaneHCID 668402-Bromo-4'-nitroacetophenoneHCID 81531Diisopropylethylamine

Product 1

HCID 574161124-Ethyl-2-(4-nitrophenyl)morpholine

Procedure

Combined 2-Bromo-1-(4-nitro-phenyl)-ethanone (5.0 g, 0.020 mol) with Methylene chloride (100 mL, 2 mol) and treated with 2-Ethylamino-ethanol (2.0 mL, 0.020 mol) and N,N-Diisopropylethylamine (3.6 mL, 0.021 mol), stirred at rt, 3 h. Treated the mixture with Triethylsilane (10.33 mL, 0.06468 mol) and then Trifluoroacetic Acid (52.5 mL, 0.681 mol) and heated to 40° C. and stirred under nitrogen overnight. Concentrated and partitioned between ice/water and heptane, stirred vigorously for 10 min. Decanted off the heptane to remove silyl byproducts, repeated. Basified with solid K2CO3. Extracted with EtOAc, the organics were washed with brine, dried (MgSO4), filtered and concentrated onto Celite and purified by ISCO chromatography (80 g, SiO2, gradient elution: 100% Hex to 100% EtOAc to 10% MeOH/EtOac), (+/−)-4-Ethyl-2-(4-nitro-phenyl)-morpholine was isolated as red waxy solid (2.45 grams). 1H-NMR (CDCl3) δ 8.22 (d, J=8.8 Hz, 2H), 7.76 (d, J=8.8 Hz, 2H), 4.69 (dd, J=10.5, 2.3 Hz, 1H), 4.10 (dd, J=11.5, 2.0, 1H), 3.90-3.84 (m, 1H), 4.11-4.08 (m, 1H), 3.00 (d, J=11.5 Hz, 1H), 2.87 (d, J=9.9 Hz, 1H), 2.48 (dd, J=7.2, 14.4 Hz, 2H), 2.27-2.20 (m, 1H), 1.99 (t, J=10.7 Hz, 1H), 1.13 (t, J=7.2 Hz, 3H); LC/MS (ESI+): 237 (M+H).

Workup

  1. stirringstirred under nitrogen overnight
  2. concentrationConcentrated
  3. custompartitioned between ice/water and heptane
  4. stirringstirred vigorously for 10 min
  5. customDecanted off the heptane
  6. customto remove silyl byproducts
  7. extractionExtracted with EtOAc
  8. washthe organics were washed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated onto Celite
  12. custompurified by ISCO chromatography (80 g, SiO2, gradient elution: 100% Hex to 100% EtOAc to 10% MeOH/EtOac)

Sources & evidence

ORD record
ord-eb060d3281c34387a4603bb827a0b65f
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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