Cesium carbonate → HCID 44193424, compound

HRID 1850006Notes

Reaction equation

HRID 1850006 reaction equation
Br[C:2]([CH3:16])([CH3:15])[C:3]([NH:5][C:6]1[O:10][N:9]=[C:8]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:7]=1)=[O:4].[NH2:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.C(Cl)Cl>[C:11]([C:8]1[CH:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:16])([NH:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[CH3:15])[O:10][N:9]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 4192234-AminotetrahydropyranHCID 59703982HCID 59703982, compound

Product 1

HCID 44193424HCID 44193424, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-bromo-N-(3-tert-butyl-isoxazol-5-yl)-2-methyl-propionamide (prepared according to method B, step 1, 2.0 g, 6.92 mmol) in anhydrous THF (40 mL) are added 4-aminotetrahydropyran (0.70 g, 6.92 mmol) and Cs2CO3. The reaction is heated to 60° C. for 48 h. After cooling the reaction mixture is partitioned between DCM (100 mL) and water (100 mL). The organic layer is separated and dried over Na2SO4. Filtration and concentration of the filtrate gives a yellow oil. The oil is dissolved in DCM and extracted with 1M aqueous HCl solution. The acidic aqueous extract is basified with 5M aqueous NaOH solution and extracted with DCM (3×100 mL). The combined organic extracts are dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure to give N-(3-tert-butyl-isoxazol-5-yl)-2-methyl-2-(tetrahydro-pyran-4-ylamino)-propionamide (0.89 g, 42%). m/z 310 [M+H+]. Conversion into its hydrochloride salt is achieved upon treatment with 1M HCl solution in diethyl ether (2.89 mL).

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customis partitioned between DCM (100 mL) and water (100 mL)
  3. customThe organic layer is separated
  4. dry with materialdried over Na2SO4
  5. filtrationFiltration and concentration of the filtrate
  6. customgives a yellow oil
  7. extractionextracted with 1M aqueous HCl solution
  8. extractionThe acidic aqueous extract
  9. extractionextracted with DCM (3×100 mL)
  10. dry with materialThe combined organic extracts are dried over Na2SO4
  11. filtrationfiltered
  12. concentrationthe filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-2afb5acc92dd41019b5605396cde3d59
Source dataset
uspto-grants-2015_02
Patent number
US08957063B2

Reaction notes

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