Hydrochloric Acid → 3-Cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl ester

HRID 2353341Notes

Reaction equation

HRID 2353341 reaction equation
[Li]CCCC.[N+:6]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][CH:10]=1)([O-:8])=[O:7].[CH:21]1([CH2:26]I)[CH2:25][CH2:24][CH2:23][CH2:22]1.Cl>C1COCC1.CN1C(=O)N(C)CCC1>[CH2:19]([O:18][C:16](=[O:17])[CH:15]([C:12]1[CH:11]=[CH:10][C:9]([N+:6]([O-:8])=[O:7])=[CH:14][CH:13]=1)[CH2:26][CH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)[CH3:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 79517Ethyl 4-nitrophenylacetateHCID 2762531(Iodomethyl)cyclopentaneHCID 178418339Butyllithium

Product 1

HCID 114718493-Cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 22565281tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinoneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a 1 L round bottom flask containing 250 mL of 9:1 THF/DMPU at −78C is added under nitrogen 11 mL (78.6 mmol) anhydrous DIEA followed by rapid addition of 32 mL of 2.5M n-BuLi in hexanes. After 10 min at −78° C. a solution of 15.4 g (74 mmol) of p-nitro-phenylacetic acid, ethyl ester in 100 mL of 9:1 THF/DMPU is added dropwise over 30 min. A deep purple solution results, and the reaction mixture is stirred at −78° C. for 30 min and then cyclopentyl methyl iodide (17.6 g, 78 mmol) in 50 mL of 9:1 THF/DMPU is added. The reaction is stirred while warming slowly to RT temperature overnight. The mixture is poured into 1 L of 1 N HCl (aq) and extracted twice with methyl-t-butylether (MTBE). The combined MTBE extracts are washed with brine, dried over anhydrous magnesium sulfate, filtered and reduced to an orange oil. Flash chromatography over silica eluting with 4:1 hexane/MTBE affords 3-cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl ester as an orange oil: 1H NMR (400 MHz, CDCl3) δ 1.0-1.1 (m, 2H), 1.2 (t, 3H, J=7.2), 1.4-1.8 (m, 5H), 1.8-1.9 (m, 2H), 2.1-2.25 (m, 2H), 3.74 (t, 1H, J=7.8), 4.1 (m, 2H), 7.51 (d, 2H, J=8.8), 8.19 (d, 2H, J=8.8).

Workup

  1. additionis added under nitrogen 11 mL (78.6 mmol) anhydrous DIEA
  2. customA deep purple solution results
  3. stirringThe reaction is stirred
  4. temperaturewhile warming slowly to RT temperature overnight
  5. extractionextracted twice with methyl-t-butylether (MTBE)
  6. washThe combined MTBE extracts are washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered

Sources & evidence

ORD record
ord-72804d6c0d9645718e0dd0791ce489dd
Source dataset
uspto-grants-2010_07
Patent number
US07750020B2

Reaction notes

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