1,2-Dichloroethane → (R)-5-tert-butyl-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)isoxazole-3-carboxamide

HRID 511856

Reaction equation

HRID 511856 reaction equation
Cl.Cl.[F:3][C:4]([F:17])([F:16])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([C@H:13]([NH2:15])[CH3:14])=[N:11][CH:12]=1.[C:18]([C:22]1[O:26][N:25]=[C:24]([C:27](O)=[O:28])[CH:23]=1)([CH3:21])([CH3:20])[CH3:19].C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>ClCCl.CO>[C:18]([C:22]1[O:26][N:25]=[C:24]([C:27]([NH:15][C@@H:13]([C:10]2[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]([F:3])([F:16])[F:17])=[CH:12][N:11]=2)[CH3:14])=[O:28])[CH:23]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 173896645-tert-Butyl-1,2-oxazole-3-carboxylic acidHCID 66892447(1R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethan-1-amine dihydrochloride

Product 1

HCID 67289670(R)-5-tert-butyl-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)isoxazole-3-carboxamideYield 75%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethanamine 2HCl salt (18 mg, 0.06 mmol) and 5-tert-butylisoxazole-3-carboxylic acid (10 mg, 0.06 mmol) in dichloromethane (2 mL) were added triethylamine (19 mg, 0.18 mmol), EDC (19 mg, 0.1 mmol) and HOBT (9.4 mg, 0.06 mmol) respectively. The reaction mixture was stirred at room temperature for 18 hours. The solvent was evaporated by N2-flow. The resulting residue was dissolved into ethyl acetate and water was added to the mixture. The organic layer was then washed with brine, and dried over sodium sulfate. After the filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give the residue. The residue was diluted with methanol and applied onto a strong cation exchange cartridge (BondElute(registered trademark) SCX, 1 g/6 mL, Varian Inc.), and the solid phase matrix was rinsed with methanol (6 mL). The crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL) and concentrated in vacuo. The residue was purified by preparative LC-MS to give 17 mg, (75% yield) of the title compound.

Workup

  1. customThe solvent was evaporated by N2-flow
  2. dissolutionThe resulting residue was dissolved into ethyl acetate and water
  3. additionwas added to the mixture
  4. washThe organic layer was then washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter the filtration
  7. customto separate solvent and sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customto give the residue
  10. wash), and the solid phase matrix was rinsed with methanol (6 mL)
  11. washThe crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL)
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by preparative LC-MS

Sources & evidence

ORD record
ord-8bb666ab618f4b7ba810fee4684aeaf2
Source dataset
uspto-grants-2015_08
Patent number
US09101616B2

Linked notes

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