Ammonium Hydroxide → (R)-tert-butyl 2-(5-methoxycarbonylthiophen-2-yl)pyrrolidine-1-carboxylate

HRID 564219

Reaktionsgleichung

Reaktionsgleichung von HRID 564219
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1C[C@H]2N(C[C@H]3[C@@H]4CCCCN4C[C@@H]2C3)CC1.C([Li])(CC)C.Br[C:36]1[S:40][C:39]([C:41]([O:43][CH3:44])=[O:42])=[CH:38][CH:37]=1.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[OH-].[NH4+]>COC(C)(C)C.C1CCCCC1.CCOCC.[Cl-].[Zn+2].[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:44][O:43][C:41]([C:39]1[S:40][C:36]([C@H:12]2[CH2:11][CH2:10][CH2:9][N:8]2[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])=[CH:37][CH:38]=1)=[O:42]

Komponenten

12

Edukt 6

HCID 14923Ammonium HydroxideHCID 605713Methyl 5-bromothiophene-2-carboxylateHCID 643455N-Boc-pyrrolidineHCID 644020SparteineHCID 44558591Tri-t-butylphosphine fluoroborateHCID 178418400CID 53628100

Produkt 1

HCID 66758892(R)-tert-butyl 2-(5-methoxycarbonylthiophen-2-yl)pyrrolidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 167845palladium(II) acetateKatalysatorHCID 3007855ZincchlorideKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 8078CyclohexaneLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Versuchsvorschrift

To a solution of N-Boc-pyrrolidine (3 mL) and (−)-sparteine (3.9 mL) in tert-butyl methyl ether (36 mL) at −78° C. was added 1.4M sec-butyl lithium in cyclohexane (12.21 mL). The solution was stirred for 3 hours and 1M zinc chloride in ether (10.2 mL) was added. The mixture was stirred for 30 minutes and warmed to ambient temperature for 30 minutes. Methyl 5-bromothiophene-2-carboxylate (3.15 g), tri-tert-butylphosphine tetrafluoroborate (249 mg) and palladium(II) acetate (153 mg) were added, and the mixture was stirred at ambient temperature overnight, treated with concentrated ammonium hydroxide (1 mL) and stirred for 30 minutes, and filtered through diatomaceous earth (Celite®). The filtrate was washed with 0.5M hydrochloric acid solution and water and concentrated. The concentrate was flash chromatographed on silica gel with ethyl acetate/hexane.

Aufarbeitung

  1. stirringThe mixture was stirred for 30 minutes
  2. stirringthe mixture was stirred at ambient temperature overnight
  3. stirringstirred for 30 minutes
  4. filtrationfiltered through diatomaceous earth (Celite®)
  5. washThe filtrate was washed with 0.5M hydrochloric acid solution and water
  6. concentrationconcentrated
  7. customchromatographed on silica gel with ethyl acetate/hexane

Quellen und Nachweise

ORD-Eintrag
ord-6c310ccc24894e758f571d8f23d9781f
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067613B2

Verknüpfte Notizen

Wird geladen…