N-Boc-pyrrolidine → (R)-tert-butyl 2-(2-oxoindolin-4-yl)pyrrolidine-1-carboxylate

HRID 529136

Reaktionsgleichung

Reaktionsgleichung von HRID 529136
C([Li])(CC)C.[N:6]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1.Br[C:19]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:20]=1[CH2:21][C:22](=[O:28])[NH:23]2.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>CC(OC)(C)C.[Cl-].[Zn+2].[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[O:28]=[C:22]1[CH2:21][C:20]2[C:24](=[CH:25][CH:26]=[CH:27][C:19]=2[C@H:7]2[CH2:8][CH2:9][CH2:10][N:6]2[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[NH:23]1

Komponenten

9

Edukt 4

HCID 643455N-Boc-pyrrolidineHCID 27631904-bromo-2,3-dihydro-1H-indol-2-oneHCID 44558591Tri-t-butylphosphine fluoroborateHCID 178418400CID 53628100

Produkt 1

HCID 69812735(R)-tert-butyl 2-(2-oxoindolin-4-yl)pyrrolidine-1-carboxylateAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 3007855ZincchlorideKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

sec-Butyl lithium (25.3 mL, 35.4 mmol) was added into a solution of tert-butyl 1-pyrrolidinecarboxylate (6.2 mL, 35.4 mmol) and (−)-spartiene (8.29 g, 35.4 mmol) in MTBE (100 mL) at −78° C. The mixture was stirred for 1 hour at −78° C. Zinc chloride solution (35.4 mL, 35.4 mmol) was added, and the reaction was stirred for 15 minutes at −78° C. The reaction was allowed to warm up to room temperature. 4-Bromoindolin-2-one (5.00 g, 23.6 mmol), palladium (II) acetate (0.53 g, 2.4 mmol) and tri-tert-butylphosphine tetrafluoroborate (0.68 g, 2.4 mmol) was added into the reaction mixture. The reaction was stirred for 12 hours at room temperature. The reaction mixture was poured into EtOAc (200 mL), and the suspension was filtered with a pad of celite. The filtrate was concentrated, and the residue was purified by flash chromatography (silica gel eluted with 4:1 hexanes:ethyl acetate) to give (R)-tert-butyl 2-(2-oxoindolin-4-yl)pyrrolidine-1-carboxylate (1.9 g, 27%) as a solid. 1H NMR (CDCl3, 400 MHz) δ 7.80 (s, 1H), 7.10-7.20 (m, 1H), 6.75-6.82 (m, 1H), 6.62-6.78 (m, 1H), 4.65-4.93 (m, 1H), 3.34-3.73 (m, 4H), 2.20-2.40 (m, 1H), 1.84-2.00 (m, 2H), 1.68-1.83 (m, 1H), 1.45 (2, 4H), 1.14 (s, 5H). MS (APCI+) [M+H]+ 303.

Aufarbeitung

  1. stirringthe reaction was stirred for 15 minutes at −78° C
  2. temperatureto warm up to room temperature
  3. stirringThe reaction was stirred for 12 hours at room temperature
  4. filtrationthe suspension was filtered with a pad of celite
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by flash chromatography (silica gel eluted with 4:1 hexanes:ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-dcb387eb90b84d108a43c0e3b21a26fe
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346805B2

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