Morpholine → 4-(3-Nitro-5-trifluoromethyl-benzoyl)-morpholine

HRID 1446698Notes

Reaction equation

HRID 1446698 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7]([OH:9])=O)([O-:3])=[O:2].ON1C2N=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1>C1COCC1.C(Cl)Cl>[N:42]1([C:7]([C:6]2[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[O:9])[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10868DicyclohexylcarbodiimideHCID 181649HOAtHCID 6166023-Nitro-5-(trifluoromethyl)benzoic acid

Product 1

HCID 219549894-(3-Nitro-5-trifluoromethyl-benzoyl)-morpholine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 3-nitro-5-trifluoromethyl-benzoic acid (2.9 g, 12.6 mmol) and 1-hydroxy-7-azabenzotriazole (25 mL of 0.5 M solution in DMF) in THF. Add 1,3-dicyclohexylcarbodiimide (2.6 g, 12.6 mmol) and morpholine (1 g, 11 mmol). Stir the mixture for 48-72 hours at room temperature. Dilute the resulting suspension with DCM and quench with saturated aqueous ammonium chloride. Wash the organic layer further by aqueous saturated sodium chloride and water, dry (MgSO4) and concentrate to a yellow-white residue. Purify by silica gel column chromatography, with a gradient from 100% hexane to 50% hexane in ethyl acetate, yielding the title compound as 2.5 g white solid (75% yield). LCMS (ES), m/z 305 (M+1).

Workup

  1. customquench with saturated aqueous ammonium chloride
  2. washWash the organic layer further by aqueous saturated sodium chloride and water
  3. dry with materialdry (MgSO4)
  4. concentrationconcentrate to a yellow-white residue
  5. customPurify by silica gel column chromatography, with a gradient from 100% hexane to 50% hexane in ethyl acetate

Sources & evidence

ORD record
ord-99377fc845c94ae491c48df1e4602492
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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