4-Methylmorpholine → HCID 14821719, Verbindung

HRID 572030Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 572030
[CH2:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C:21](O)=[O:22])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>O1CCCC1.O>[CH2:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[C@H:11]([CH2:21][OH:22])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 11860409Boc-Hyp(Bzl)-OH

Produkt 1

HCID 14821719HCID 14821719, VerbindungAusbeute 82,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of (2S,4R)-4-(benzyloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (5.00 g, 15.56 mmol) in tetrahydrofuran (50 mL) at −10° C. was added N-methylmorpholine (1.882 mL, 17.11 mmol). To this solution was added slowly isobutyl chloroformate (2.34 g, 2.25 mL, 17.11 mmol). The resulting mixture was stirred for 30 minutes and filtered, and the filtrate was added to a solution of sodium borohydride (1.18 g, 31.1 mmol) in water (1.5 mL) at 0° C. The resulting mixture was stirred at 0° C. for 30 minutes, and the reaction was quenched by the addition of a saturated solution of NH4Cl. The mixture was extracted with ethyl acetate, and the organic extract was washed with brine, dried with MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-2% methanol in dichloromethane to give the title compound as a colorless oil (3.93 g, 82%). 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 7.36 (d, J=7.4 Hz, 2 H), 7.30 (t, J=7.3 Hz, 2 H), 7.23 (t, J=7.2 Hz, 1 H), 4.50 (s, 2 H), 4.20-4.29 (m, 2 H), 3.92-4.00 (m, 1 H), 3.80-3.87 (m, 2 H), 3.50-3.59 (m, 1 H), 2.16-2.30 (m, 2 H), 1.47 (s, 9 H).

Aufarbeitung

  1. filtrationfiltered
  2. stirringThe resulting mixture was stirred at 0° C. for 30 minutes
  3. customthe reaction was quenched by the addition of a saturated solution of NH4Cl
  4. extractionThe mixture was extracted with ethyl acetate
  5. extractionthe organic extract
  6. washwas washed with brine
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-2% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-931a76cc59b247ffb2c36b9f6620d265
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029361B2

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