4-Methylmorpholine → 2-(4-Bromo-phenyl)-N-(6-methyl-4-trifluoromethyl-pyridin-2-yl)-acetamide

HRID 1446716Notes

Reaction equation

HRID 1446716 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.[CH3:12][C:13]1[N:18]=[C:17]([NH2:19])[CH:16]=[C:15]([C:20]([F:23])([F:22])[F:21])[CH:14]=1.CN1CCOCC1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:19][C:17]2[CH:16]=[C:15]([C:20]([F:22])([F:21])[F:23])[CH:14]=[C:13]([CH3:12])[N:18]=2)=[O:11])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 74654Benzeneacetic acid, 4-bromo-HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 184285216-Methyl-4-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 685463602-(4-Bromo-phenyl)-N-(6-methyl-4-trifluoromethyl-pyridin-2-yl)-acetamideYield 62.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 4-bromo-phenylacetic acid (660 mg, 3.07 mmol) and 6-methyl-4-trifluoromethyl-pyridin-2-ylamine (500 mg, 2.84 mmol) in 10 mL dry THF. Add 4-methyl morpholine (345 mg, 0.375 mL, 3.4 mmol), stir a few minutes under nitrogen atmosphere, then add DMTMM (865 mg, 3.12 mmol) and stir the pale yellow slurry overnight. Dilute slurry with 90 mL EtOAc, wash twice each with saturated aqueous NaHCO3 and aqueous saturated sodium chloride, then dry the organic layer over MgSO4 and concentrate to give an ivory crystalline solid. Purify this solid on a 120 g silica cartridge with 0→5% EtOAc in dichloromethane to give 660 mg (62%) of the title compound as a white crystalline solid. LCMS (ES) m/z 373/375 (M+1).

Workup

  1. washwash twice each with saturated aqueous NaHCO3 and aqueous saturated sodium chloride
  2. dry with materialdry the organic layer over MgSO4
  3. concentrationconcentrate
  4. customto give an ivory crystalline solid
  5. customPurify this solid on a 120 g silica cartridge with 0→5% EtOAc in dichloromethane

Sources & evidence

ORD record
ord-75b57fb05d714b96bb8c64245e4f114e
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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