Methanol → (3S,5S)-5-(3-Chloro-2-fluoro-benzylcarbamoyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

HRID 1527320Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1527320
Cl[Si](C)(C)C.C[OH:7].[C:8]([O:12][C:13]([N:15]1[CH2:19][C@@H:18]([C:20]#N)[CH2:17][C@H:16]1[C:22](=[O:33])[NH:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:26]=1[F:32])=[O:14])([CH3:11])([CH3:10])[CH3:9].[C:34](OC(OC(C)(C)C)=O)(OC(C)(C)C)=[O:35]>C(Cl)Cl>[CH3:34][O:35][C:20]([C@H:18]1[CH2:17][C@@H:16]([C:22](=[O:33])[NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:26]=2[F:32])[N:15]([C:13]([O:12][C:8]([CH3:9])([CH3:11])[CH3:10])=[O:14])[CH2:19]1)=[O:7]

Komponenten

6

Edukt 4

HCID 887MethanolHCID 6397ChlorotrimethylsilaneHCID 90495Di-tert-butyl dicarbonateHCID 68283946(2S,4S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 68284043(3S,5S)-5-(3-Chloro-2-fluoro-benzylcarbamoyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Chlorotrimethylsilane (5.66 mL, 44.8 mmol) was added dropwise to dry MeOH (7.6 mL) at 0° C. followed by a solution of (2S,4S)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (900 mg, 2.36 mmol) in dry CH2Cl2 (6.7 mL) and the resulting mixture was stirred at RT for 5 h. The mixture was cooled to 0° C., quenched with a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2 (×3). To the organic extracts was added di-tert-butyl dicarbonate (514 mg, 2.36 mmol) at RT and the resulting solution was stirred overnight. The reaction mixture was concentrated in vacuo and the crude material purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1) to give the expected compound. tR (HPLC conditions a): 3.50 min.

Aufarbeitung

  1. temperatureThe mixture was cooled to 0° C.
  2. customquenched with a saturated aqueous solution of NaHCO3
  3. extractionextracted with CH2Cl2 (×3)
  4. stirringthe resulting solution was stirred overnight
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe crude material purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-6bd16d27bf8e41218f03e5059dcfc77b
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09085555B2

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