Ethyl 4-nitrophenylacetate → 3-Cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl ester

HRID 398569Notes

Reaction equation

HRID 398569 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH2:9]([O:11][C:12](=[O:23])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[CH3:10].I[CH2:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O.CN(C)P(N(C)C)(N(C)C)=O>[CH2:9]([O:11][C:12](=[O:23])[CH:13]([C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[CH2:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1)[CH3:10]

Participants

6

Reactant 3

HCID 79517Ethyl 4-nitrophenylacetateHCID 2724682Lithium diisopropylamideHCID 2762531(Iodomethyl)cyclopentane

Product 1

HCID 114718493-Cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl esterYield 77.2%

Reagents, catalysts & solvents 2

HCID 12679HexamethylphosphoramideSolventHCID 86583969tetrahydrofuran HMPASolvent

Conditions

Temperature
-78 °C

Procedure

A solution of freshly prepared lithium diisopropylamide (430.55 mL of a 0.3M stock solution, 129.16 mmol) cooled to −78° C. was treated with (4-nitro-phenyl)-acetic acid ethyl ester (prepared as in Example 22A, 26.32 g, 125.83 mmol) in tetrahydrofuran/hexamethylphosphoramide (312.5 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min. Iodomethylcyclopentane (27.75 g, 132.1 mmol) was then added in hexamethylphosphoramide (27.75 mL). The mixture was stirred at −78° C. for 4 h. The reaction was then warmed to 25° C. and was stirred at 25° C. for 16 h. The reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (250 mL). This mixture was concentrated in vacuo. The residue was diluted with water (250 mL) and extracted with ethyl acetate (3×300 mL). The combined organic layers were washed with a saturated aqueous lithium chloride solution (2×250 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 98/2 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-nitro-phenyl)-propionic acid ethyl ester (28.30 g, 77.2%) as a yellow oil: EI-HRMS m/e calcd for C16H21NO4 (M+) 291.1470, found 291.1470.

Workup

  1. stirringThe mixture was stirred at −78° C. for 4 h
  2. temperatureThe reaction was then warmed to 25° C.
  3. stirringwas stirred at 25° C. for 16 h
  4. customThe reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (250 mL)
  5. concentrationThis mixture was concentrated in vacuo
  6. additionThe residue was diluted with water (250 mL)
  7. extractionextracted with ethyl acetate (3×300 mL)
  8. washThe combined organic layers were washed with a saturated aqueous lithium chloride solution (2×250 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6ac4d8f8c2df445f8255980db1b9a1c4
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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