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

HRID 1854321Notes

Reaction equation

HRID 1854321 reaction equation
[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

Participants

8

Reactant 4

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

Product 2

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-b121c17d5c9c4a1291b29900a829c7b4
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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