Sodium hydride → ethyl 4-[(S)-3-(t-butoxycarbonylamino)-2-oxopyrrolidin-1-ylmethyl]-3-trifluoromethylbenzoate

HRID 13765

Reaktionsgleichung

Reaktionsgleichung von HRID 13765
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][NH:11][C:10]1=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:18][C:19]1[CH:29]=[CH:28][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][C:20]=1[C:30]([F:33])([F:32])[F:31]>O1CCCC1.CN(C)C=O.O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([CH2:18][C:19]2[CH:29]=[CH:28][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][C:20]=2[C:30]([F:31])([F:33])[F:32])[C:10]1=[O:14])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 10750535(S)-tert-Butyl (2-oxopyrrolidin-3-yl)carbamateHCID 23073576Ethyl 4-(bromomethyl)-3-(trifluoromethyl)benzoate

Produkt 1

HCID 68690133ethyl 4-[(S)-3-(t-butoxycarbonylamino)-2-oxopyrrolidin-1-ylmethyl]-3-trifluoromethylbenzoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 21974620tetrahydrofuran N,N-dimethylformamideLösungsmittel

Versuchsvorschrift

669 mg of (S)-3-(t-butoxycarbonylamino)pyrrolidin-2-one (J. Med. Chem., 1999, 42, 3557-3571) was dissolved in 30 ml of tetrahydrofuran/N,N-dimethylformamide (9:1) and the mixture was stirred under ice cooling. 60% sodium hydride was added thereto and the mixture was stirred for 20 minutes. A solution (3 ml) of ethyl 4-(bromomethyl)-3-trifluoromethylbenzoate (Reference Example 2 (step 2)) in tetrahydrofuran was added dropwise, followed by stirring at room temperature for 6 hours after removing an ice bath. The reaction solution was poured into an aqueous saturated ammonium chloride solution, followed by extraction with ethyl acetate twice, and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 867 mg of the objective compound as pale yellow crystals.

Aufarbeitung

  1. stirringthe mixture was stirred for 20 minutes
  2. stirringby stirring at room temperature for 6 hours
  3. customafter removing an ice bath
  4. additionThe reaction solution was poured into an aqueous saturated ammonium chloride solution
  5. extractionfollowed by extraction with ethyl acetate twice
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-20807a0cd3ad4b0d9de1996e1d5c24a7
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728131B2

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