Sodium hydride → 2-(4-Nitrophenyl)-4-tosylmorpholine

HRID 1485219Notes

Reaction equation

HRID 1485219 reaction equation
[OH:1][CH:2]([C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)[CH2:3][NH:4][S:5]([C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)(=[O:7])=[O:6].[H-].[Na+].FC(F)(F)S([O-])(=O)=O.Br[CH2:35][CH2:36][S+](C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[NH4+]>C(Cl)Cl.O.C(OCC)(=O)C>[N+:21]([C:18]1[CH:19]=[CH:20][C:15]([CH:2]2[O:1][CH2:36][CH2:35][N:4]([S:5]([C:8]3[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=3)(=[O:7])=[O:6])[CH2:3]2)=[CH:16][CH:17]=1)([O-:23])=[O:22]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 25193077(2-Bromoethyl)diphenylsulfonium TrifluoromethanesulfonateHCID 68282567N-(2-Hydroxy-2-(4-nitrophenyl)ethyl)-4-methylbenzenesulfonamide

Product 1

HCID 682828702-(4-Nitrophenyl)-4-tosylmorpholine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-(2-Hydroxy-2-(4-nitrophenyl)ethyl)-4-methylbenzenesulfonamide (I84) (0.610 g, 1.34 mmol) was sonicated in DCM (20 mL) for five minutes and cooled to 0° C. under nitrogen. A 60% dispersion of NaH (0.220 g, 5.44 mmol) was added and the mixture stirred for five minutes before (2-bromoethyl)diphenylsulfonium trifluoromethanesulfonate (1.21 g, 2.72 mmol) was added. The mixture was stirred for 17 hours, allowing the cooling bath to come to room temperature over this time. Ethyl acetate (200 mL), saturated ammonium chloride (80 mL) and water (20 mL) were added and the layers separated. The aqueous phase was extracted with ethyl acetate (2×100 mL) and the combined ethyl acetate phases were washed with brine, dried (sodium sulfate) and evaporated. The residue was chromatographed (Isolera, 40 g silica cartridge, 0-40% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I85) (433 mg, 88%) as a white solid; 1H NMR (400 MHz, CDCl3) b 8.22-8.18 (m, 2H), 7.63-7.59 (m, 2H), 7.52-7.48 (m, 2H), 7.33 (dd, J=8.5, 0.6 Hz, 2H), 4.71 (dd, J=10.2, 2.6 Hz, 1H), 4.10 (ddd, J=11.6, 3.4, 1.4 Hz, 1H), 3.87 (td, J=11.6, 2.7 Hz, 1H), 3.82-3.77 (m, 1H), 3.65 (ddt, J=11.6, 2.8, 1.6 Hz, 1H), 2.51 (td, J=11.6, 3.4 Hz, 1H), 2.43 (s, 3H), 2.18 (dd, J=11.5, 10.3 Hz, 1H). LCMS Method C: rt 6.20 min; m/z 363.0 [M+H]+.

Workup

  1. additionwas added
  2. customto come to room temperature over this time
  3. customthe layers separated
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
  5. washthe combined ethyl acetate phases were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. customevaporated
  8. customThe residue was chromatographed (Isolera, 40 g silica cartridge, 0-40% ethyl acetate/petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-cbf94e2f5b864153af8f5b6c9f97e9cd
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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