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

HRID 2190072Notes

Reaction equation

HRID 2190072 reaction equation
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

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalystHCID 8857Ethyl AcetateSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b6ff8abee4ba4cfb81ba31626642f308
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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