Sulfuric Acid → 2-(4-Chlorophenyl)-2-(4-iodophenyl)morpholine

HRID 924756Notes

Reaction equation

HRID 924756 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:15]2[CH:20]=[CH:19][C:18]([I:21])=[CH:17][CH:16]=2)([OH:14])[CH2:9][NH:10][CH2:11][CH2:12]O)=[CH:4][CH:3]=1.OS(O)(=O)=O>C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][CH:16]=3)[O:14][CH2:12][CH2:11][NH:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 1118Sulfuric Acid2×HCID 593319671-(4-Chloro-phenyl)-2-(2-hydroxy-ethylamino)-1-(4-iodo-phenyl)-ethanol

Product 1

HCID 593319352-(4-Chlorophenyl)-2-(4-iodophenyl)morpholineYield 43.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-(4-chloro-phenyl)-2-(2-hydroxy-ethylamino)-1-(4-iodo-phenyl)-ethanol (701 mg, 1.68 mmol) in DCM (10 mL) was treated with concentrated H2SO4 (0.1 mL, 1.9 mmol). After 20 hours, another portion of H2SO4 (1.0 mL, 19 mmol) was added and the mixture stirred for a further 2 hours. The mixture was diluted with ethyl acetate and washed with saturated potassium carbonate and brine then dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (SiO2), eluting with 0.5% triethylamine in ethyl acetate to afford the title compound (290 mg, 43%); LCMS (PS-A2) Rt 2.40 min [M+H]+ 400.

Workup

  1. washwashed with saturated potassium carbonate and brine
  2. dry with materialthen dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (SiO2)
  6. washeluting with 0.5% triethylamine in ethyl acetate

Sources & evidence

ORD record
ord-4fc6204b68b940058157a26450d36757
Source dataset
uspto-grants-2016_03
Patent number
US09283226B2

Reaction notes

Loading…