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

HRID 2190072

반응식

HRID 2190072 반응식
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

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 3007855Zincchloride촉매HCID 8857Ethyl Acetate용매HCID 15413tert-Butyl methyl ether용매

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b6ff8abee4ba4cfb81ba31626642f308
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324221B2

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