4-Methoxyphenylacetic Acid → HCID 22315103, compound

HRID 398629Notes

Reaction equation

HRID 398629 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=[O:19])=[CH:13][CH:12]=1.I[CH2:22][CH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>O1CCCC1.CN1CCCN(C)C1=O.CN1CCCN(C)C1=O>[CH:23]1([CH2:22][CH:17]([C:14]2[CH:13]=[CH:12][C:11]([O:10][CH3:9])=[CH:16][CH:15]=2)[C:18]([OH:20])=[O:19])[CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 76904-Methoxyphenylacetic AcidHCID 2724682Lithium diisopropylamideHCID 2762531(Iodomethyl)cyclopentane

Product 1

HCID 22315103HCID 22315103, compoundYield 43.8%

Reagents, catalysts & solvents 2

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-SolventHCID 22565281tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinoneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of freshly prepared lithium diisopropylamide (58.5 mL of a 0.93M stock solution, 53.2 mmol) cooled to −78° C. was treated with (4-methoxy-phenyl)-acetic acid (4.21 g, 25.35 mmol) in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (25.3 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min. At this time, the reaction was treated with a solution of iodomethylcyclopentane (5.85 g, 27.8 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 mL). The reaction mixture was stirred at −78° C. for 45 min and at 0° C. for 1 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 saturated aqueous ammonium chloride solution (10 mL). The excess solvent was removed in vacuo. The residue was acidified to pH=1 with a 1N aqueous hydrochloric acid solution. This mixture was poured into water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with a saturated aqueous lithium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 70/30 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methoxy-phenyl)-propionic acid (2.76 g, 43.8%) as a yellow solid: mp 119-121° C.; EI-HRMS m/e calcd for C15H20O3 (M+) 248.1412 found 248.1415.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 45 min and at 0° C. for 1 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 saturated aqueous ammonium chloride solution (10 mL)
  5. customThe excess solvent was removed in vacuo
  6. additionThis mixture was poured into water (50 mL)
  7. extractionextracted with ethyl acetate (3×50 mL)
  8. washThe combined organic layers were washed with a saturated aqueous lithium chloride solution (1×100 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0fc3c0b469024bbe9c404704c295121a
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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