Potassium Carbonate → Ethyl 3-({[3-(4-chlorophenyl)-isoxazol-5-yl]methyl}amino)-3-methylbutanoate

HRID 1485120Notes

Reaction equation

HRID 1485120 reaction equation
Cl.[NH2:2][C:3]([CH3:11])([CH3:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:13][C:14]1[O:18][N:17]=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[Cl:25][C:22]1[CH:21]=[CH:20][C:19]([C:16]2[CH:15]=[C:14]([CH2:13][NH:2][C:3]([CH3:11])([CH3:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])[O:18][N:17]=2)=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21369Isoxazole, 5-bromomethyl-3-(p-chlorophenyl)-HCID 15578558Ethyl 3-amino-3-methylbutanoate hydrochloride

Product 1

HCID 118113168Ethyl 3-({[3-(4-chlorophenyl)-isoxazol-5-yl]methyl}amino)-3-methylbutanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 3-amino-3-methylbutyrate hydrochloride (333 mg) in tetrahydrofuran (4.00 mL), a solution in tetrahydrofuran (2.00 mL) of the compound (100 mg) obtained in step (2) above and potassium carbonate (406 mg) were added and the mixture was stirred at 60° C. for three days. After passing the reaction mixture through Celite (registered trademark), the filtrate was concentrated under reduced pressure and the resulting residue was roughly purified by preparative HPLC. To the resulting roughly purified product, a saturated aqueous solution of sodium hydrogencarbonate was added and extraction was conducted with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate and after removing the desiccant by filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=98:2-50:50) to give the titled compound as a colorless amorphous mass.

Workup

  1. concentrationthe filtrate was concentrated under reduced pressure
  2. customthe resulting residue was roughly purified by preparative HPLC
  3. additionTo the resulting roughly purified product, a saturated aqueous solution of sodium hydrogencarbonate was added
  4. extractionextraction
  5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  6. customafter removing the
  7. filtrationdesiccant by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=98:2-50:50)

Sources & evidence

ORD record
ord-bc78b860e859498dabe736749cb07bff
Source dataset
uspto-grants-2016_08
Patent number
US09422240B2

Reaction notes

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