Diisopropylamine → 3-Cyclopentyl-2-(4-iodo-phenyl)-propionic acid

HRID 1936236Notes

Reaction equation

HRID 1936236 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[I:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]([OH:23])=[O:22])=[CH:16][CH:15]=1.I[CH2:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>O1CCCC1.CN1CCCN(C)C1=O>[CH:26]1([CH2:25][CH:20]([C:17]2[CH:16]=[CH:15][C:14]([I:13])=[CH:19][CH:18]=2)[C:21]([OH:23])=[O:22])[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 1372144-Iodophenylacetic acidHCID 2762531(Iodomethyl)cyclopentaneHCID 178418339Butyllithium

Product 1

HCID 224653003-Cyclopentyl-2-(4-iodo-phenyl)-propionic acidYield 57.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (11.2 mL, 80.13 mmol) in tetrahydrofuran (120 mL) cooled to −78° C. was treated with a 2.5M solution of n-butyllithium in hexanes (32 mL, 80.13 mmol). This solution was stirred at −78° C. for 30 min and then treated with a solution of (4-iodo-phenyl)-acetic acid (9.67 g, 36.9 mmol) in tetrahydrofuran (88 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (29 mL). The reaction mixture was allowed to stir at −78° C. for 1 h. At this time, the reaction was treated with iodomethylcyclopentane (8.53 g, 40.6 mmol). The reaction mixture was allowed to slowly warm to 25° C. where it was stirred at 25° C. for 18 h. At this time, the reaction mixture was quenched with water (5 mL) and then concentrated in vacuo. The residue was diluted with water (800 mL) and was acidified to pH=2 with concentrated hydrochloric acid. This solution was extracted with ethyl acetate (2×800 mL). The combined organic extracts were washed with water (1×600 mL) and a saturated aqueous sodium chloride solution (1×600 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-iodo-phenyl)-propionic acid (7.34 g, 57.8%) as a white solid: mp 105-107° C.; EI-HRMS m/e calcd for C14H17IO2 (M+) 344.0273, found 344.0275.

Workup

  1. stirringto stir at −78° C. for 1 h
  2. temperatureto slowly warm to 25° C. where it
  3. stirringwas stirred at 25° C. for 18 h
  4. customAt this time, the reaction mixture was quenched with water (5 mL)
  5. concentrationconcentrated in vacuo
  6. additionThe residue was diluted with water (800 mL)
  7. extractionThis solution was extracted with ethyl acetate (2×800 mL)
  8. washThe combined organic extracts were washed with water (1×600 mL)
  9. dry with materiala saturated aqueous sodium chloride solution (1×600 mL), dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5fcd11e80ebf4eb9a21375c348a6af09
Source dataset
uspto-grants-2002_05
Patent number
US06388071B2

Reaction notes

Loading…