Methyl iodide → (2S,4R)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate

HRID 1854321Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1854321
[Li+].[CH3:2]C([N-]C(C)C)C.[CH2:9]([N:16]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:17]1[CH2:21][CH:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:19]([CH2:27][CH3:28])[CH2:18]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CI.[NH4+].[Cl-]>C1COCC1.C(Cl)Cl>[CH2:29]([N:16]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C@@H:17]1[CH2:21][C:20]([CH3:2])([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C@H:19]([CH2:27][CH3:28])[CH2:18]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1.[CH2:29]([N:16]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C@H:17]1[CH2:21][C:20]([CH3:2])([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C@@H:19]([CH2:27][CH3:28])[CH2:18]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Komponenten

8

Edukt 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 58009964Ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate

Produkt 2

HCID 58010117(2S,4R)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylateAusbeute 168,6 %HCID 58010228(2R,4S)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of LDA (1.8M in THF, 3.04 mL, 5.47 mmol,) and THF (40 mL) at about −78° C. was added ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate (1.0 g, 2.7 mmol, Preparation #EE.1) in THF (4 mL). The reaction mixture was stirred at about −78° C. for about 1 h. MeI (2.57 mL, 41.0 mmol) was added and reaction mixture was stirred at about −78° C. for about 1 h and was then warmed to about −40° C. DCM (150 mL) was added followed by saturated aqueous NH4Cl solution (50 mL). The layers were separated and the aqueous layer was extracted with DCM (2×30 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated to dryness under reduced pressure. The residue was purified by flash silica gel chromatography eluting with a gradient of 0-10% EtOAc in DCM to give (2R,4S)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate and (2S,4R)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate (0.864 g, 84%). LC/MS (Table 2, Method a) Rt=2.25 min; MS m/z: 380 (M+H)+.

Aufarbeitung

  1. customreaction mixture
  2. stirringwas stirred at about −78° C. for about 1 h
  3. temperaturewas then warmed to about −40° C
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with DCM (2×30 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe residue was purified by flash silica gel chromatography
  11. washeluting with a gradient of 0-10% EtOAc in DCM

Quellen und Nachweise

ORD-Eintrag
ord-b121c17d5c9c4a1291b29900a829c7b4
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962629B2

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