Methyl iodide → (2S,4R)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate

HRID 1854321노트

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HRID 1854321 반응식
[Li+].[CH3:2]C([N-]C(C)C)C.[CH2:9]([N:16]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:17]1[CH2:21][CH:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:19]([CH2:27][CH3:28])[CH2:18]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CI.[NH4+].[Cl-]>C1COCC1.C(Cl)Cl>[CH2:29]([N:16]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C@@H:17]1[CH2:21][C:20]([CH3:2])([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C@H:19]([CH2:27][CH3:28])[CH2:18]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1.[CH2:29]([N:16]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C@H:17]1[CH2:21][C:20]([CH3:2])([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C@@H:19]([CH2:27][CH3:28])[CH2:18]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

참가 물질

8

반응물 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 58009964Ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate

생성물 2

HCID 58010117(2S,4R)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate수율 168.6%HCID 58010228(2R,4S)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a solution of LDA (1.8M in THF, 3.04 mL, 5.47 mmol,) and THF (40 mL) at about −78° C. was added ethyl 4-(dibenzylamino)-2-ethylcyclopentanecarboxylate (1.0 g, 2.7 mmol, Preparation #EE.1) in THF (4 mL). The reaction mixture was stirred at about −78° C. for about 1 h. MeI (2.57 mL, 41.0 mmol) was added and reaction mixture was stirred at about −78° C. for about 1 h and was then warmed to about −40° C. DCM (150 mL) was added followed by saturated aqueous NH4Cl solution (50 mL). The layers were separated and the aqueous layer was extracted with DCM (2×30 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated to dryness under reduced pressure. The residue was purified by flash silica gel chromatography eluting with a gradient of 0-10% EtOAc in DCM to give (2R,4S)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate and (2S,4R)-ethyl 4-(dibenzylamino)-2-ethyl-1-methylcyclopentanecarboxylate (0.864 g, 84%). LC/MS (Table 2, Method a) Rt=2.25 min; MS m/z: 380 (M+H)+.

후처리

  1. customreaction mixture
  2. stirringwas stirred at about −78° C. for about 1 h
  3. temperaturewas then warmed to about −40° C
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with DCM (2×30 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe residue was purified by flash silica gel chromatography
  11. washeluting with a gradient of 0-10% EtOAc in DCM

출처 및 근거

ORD 기록
ord-b121c17d5c9c4a1291b29900a829c7b4
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962629B2

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