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

HRID 2204470Notes

Reaction equation

HRID 2204470 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-d8b07b90660c4348bce90514661ce1ac
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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