1-Iodopropane → (+)-3-(2,3-Difluorophenyl)-1-propylpyrrolidin-3-OL

HRID 1931823

Reaktionsgleichung

Reaktionsgleichung von HRID 1931823
[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=2[F:21])([OH:13])[CH2:9]1)[C:2]1C=CC=C[CH:3]=1.ICCC>CN(C)C=O>[F:21][C:15]1[C:16]([F:20])=[CH:17][CH:18]=[CH:19][C:14]=1[C:10]1([OH:13])[CH2:11][CH2:12][N:8]([CH2:1][CH2:2][CH3:3])[CH2:9]1

Komponenten

4

Edukt 2

HCID 336431-IodopropaneHCID 685158491-Benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol

Produkt 1

HCID 25143813(+)-3-(2,3-Difluorophenyl)-1-propylpyrrolidin-3-OLAusbeute 34,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

In a sealed tube a mixture of (+)-1-benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol (0.40 g, 1.38 mmol), dimethyl formamide (3 mL) and iodopropane (1.35 mL, 13.8 mmol) was heated under microwave irradiation at 80° C. for 45 minutes. The resulting mixture was evaporated, morpholine (2 mL) was added and the mixture was heated under micro-wave irradiation at 130° C. for 30 minutes. Aqueous sodium carbonate (10%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (2×50 mL), the combined organic phase was washed with aqueous LiCl (5%, 50 mL), dried (Na2SO4) and evaporated. Purification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 40:60 to 60:40) gave the title compound (0.115 g). [α]D=+22.8° (methanol). The amine was converted to the fumaric acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 95-98° C.; MS m/z (relative intensity, 70 eV) 241 (M+, 8), 212, (bp), 182 (41), 84 (88), 57 (24).

Aufarbeitung

  1. customThe resulting mixture was evaporated
  2. additionmorpholine (2 mL) was added
  3. temperaturethe mixture was heated under micro-wave irradiation at 130° C. for 30 minutes
  4. additionAqueous sodium carbonate (10%, 50 mL) was added
  5. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
  6. washthe combined organic phase was washed with aqueous LiCl (5%, 50 mL)
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customPurification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 40:60 to 60:40)

Quellen und Nachweise

ORD-Eintrag
ord-c802337982cd4a5694776afe5a3fc48c
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188301B2

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