Iodine → Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxypyrrolidine-1-carboxylate

HRID 1931860Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1931860
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Cl:9])[CH:3]=1.[Mg].II.[C:13]([N:20]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]>O1CCCC1>[Cl:9][C:4]1[CH:3]=[C:2]([C:22]2([OH:25])[CH2:23][CH2:24][N:20]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:21]2)[CH:7]=[C:6]([F:8])[CH:5]=1

Komponenten

6

Edukt 4

HCID 807IodineHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 27362231-Bromo-3-chloro-5-fluorobenzeneHCID 5462224Magnesium

Produkt 1

HCID 67402932Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxypyrrolidine-1-carboxylateAusbeute 50,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 1-bromo-3-chloro-5-fluorobenzene (4.0 g, 19.1 mmol) in dry tetrahydrofuran (40 mL), under nitrogen, was added magnesium turnings (0.47 g, 21.0 mmol) and a small piece of iodine. The mixture was heated with a heat-gun until the colour disappeared and then stirred at ambient temperature for 0.5 h after which a solution of 1-N-boc-3-pyrrolidinone (2.8 g, 15.3 mmol) in dry tetrahydrofuran (10 mL) was added drop wise. The reaction mixture was stirred for 0.5 h at ambient temperature and then quenched with water (70 mL). Aqueous saturated ammonium chloride (20 mL) was added and the mixture was extracted with ethyl acetate (2×100 mL). The combined organic phase was dried (MgSO4), filtered and evaporated. Purification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:1) gave the title compound (2.43 g). MS m/z (rel. intensity, 70 eV) 315 (M+, 1), 259 (14), 214 (22), 184 (13), 143 (11), 57 (bp).

Aufarbeitung

  1. temperatureThe mixture was heated with
  2. temperaturea heat-gun until the colour
  3. additionwas added drop wise
  4. customquenched with water (70 mL)
  5. additionAqueous saturated ammonium chloride (20 mL) was added
  6. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
  7. dry with materialThe combined organic phase was dried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customPurification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-fa96d30190ab4ea8ad676257e9bebc61
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188301B2

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