Phenol → 2-(4-Nitrophenyl)morpholine

HRID 1485220Notes

Reaction equation

HRID 1485220 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[O:15][CH2:14][CH2:13][N:12](S(C3C=CC(C)=CC=3)(=O)=O)[CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C1(O)C=CC=CC=1.Br.CC(O)=O>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[O:15][CH2:14][CH2:13][NH:12][CH2:11]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

4

Reactant 3

HCID 996PhenolHCID 21893785Acetic Acid Mixture with Hydrobromic AcidHCID 682828702-(4-Nitrophenyl)-4-tosylmorpholine

Product 1

HCID 125147492-(4-Nitrophenyl)morpholine

Conditions

Temperature
75 °C

Procedure

A mixture of 2-(4-Nitrophenyl)-4-tosylmorpholine (185) (430 mg, 1.19 mmol), phenol (670 mg, 7.12 mmol) and 33% HBr/AcOH (2.2 mL) was heated in a sealed tube (microwave tube, conventional heating) at 75° C. for twenty hours. The cooled mixture was concentrated and the residue loaded onto a 10 g SCX cartridge in methanol. The cartridge was washed with methanol (200 mL), then eluted with 1% methanolic methylamine (100 mL). The methylamine eluent was evaporated to give the title compound (I86) (204 mg, 83%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.27-8.18 (m, 2H), 7.57-7.51 (m, 2H), 4.63 (dd, J=10.3, 2.5 Hz, 1H), 4.13-4.04 (m, 1H), 3.82 (td, J=11.3, 3.1 Hz, 1H), 3.13 (dd, J=12.3, 2.5 Hz, 1H), 3.06-2.92 (m, 2H), 2.74 (dd, J=12.3, 10.3 Hz, 1H). LCMS Method C: rt 1.49, 1.58 min; m/z 209.1 [M+H]+.

Workup

  1. temperaturewas heated in a sealed tube
  2. concentrationThe cooled mixture was concentrated
  3. washThe cartridge was washed with methanol (200 mL)
  4. washeluted with 1% methanolic methylamine (100 mL)
  5. customThe methylamine eluent was evaporated

Sources & evidence

ORD record
ord-7aa4b52f1f704f7d8f15c5235ce8eb6d
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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