1,2-Diaminocyclohexane, trans- → (S)-tert-butyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407880Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 407880
Br[C:2]1[CH:27]=[CH:26][C:5]([O:6][C@H:7]2[CH2:11][CH2:10][N:9]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:8]2=[O:25])=[C:4]([F:28])[CH:3]=1.[CH3:29][S:30]([O-:32])=[O:31].[Na+].[C@@H]1(N)CCCC[C@H]1N>CS(C)=O>[F:28][C:4]1[CH:3]=[C:2]([S:30]([CH3:29])(=[O:32])=[O:31])[CH:27]=[CH:26][C:5]=1[O:6][C@H:7]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[C:8]1=[O:25]

Komponenten

5

Edukt 3

HCID 438061,2-Diaminocyclohexane, trans-HCID 2733271Sodium methanesulfinateHCID 86688077(S)-tert-butyl 4-(3-(4-bromo-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

Produkt 1

HCID 86688078(S)-tert-butyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylateAusbeute 89,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Versuchsvorschrift

(S)-tert-Butyl 4-(3-(4-bromo-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (1.8 g, 3.9 mmol) was dissolved in DMSO (30 mL) and purged with nitrogen. Sodium methanesulfinate (0.60 g, 5.9 mmol) and trans-cyclohexane-1,2-diamine (0.19 mL, 1.6 mmol) were added followed by Cu(I) triflate benzene complex (0.20 g, 0.39 mmol). The reaction was plunged into a 110° C. oil bath under nitrogen and stirred overnight. The reaction was cooled to ambient temperature, partitioned between water and EtOAc, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)-tert-butyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (1.6 g, 3.5 mmol, 89% yield) as a white solid.

Aufarbeitung

  1. custompurged with nitrogen
  2. customwas plunged into a 110° C.
  3. custompartitioned between water and EtOAc
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified over silica gel (100% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-b4e02b39efcb48069e57305ec78b7e96
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754226B2

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