Diisopropylamine → HCID 54445655, compound

HRID 430289Notes

Reaction equation

HRID 430289 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15](=[O:31])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[C:19]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:18]=1.I[CH2:33][CH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1>O1CCCC1.CN1CCCN(C)C1=O>[CH3:13][O:14][C:15](=[O:31])[CH:16]([C:17]1[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:24])=[O:25])=[C:19]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:18]=1)[CH2:33][CH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 2762531(Iodomethyl)cyclopentaneHCID 53951900HCID 53951900, compoundHCID 178418339Butyllithium

Product 1

HCID 54445655HCID 54445655, compoundYield 67.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (951 μL, 6.79 mmol) in dry tetrahydrofuran (6 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2 mL) was cooled to −78° C. under nitrogen and then treated with a 2.5M solution of n-butyllithium in hexanes (2.5 mL, 6.79 mmol). The resulting reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of (3,4-bis-methanesulfonyl-phenyl)-acetic acid methyl ester (1.89 g, 6.17 mmol) in dry tetrahydrofuran (12 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (4 mL). The resulting reaction mixture was allowed to stir at −78° C. for 1 h, at which time, a solution of iodomethylcyclopentane (1.56 g, 7.40 mmol) in a small amount of dry tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to 25° C. where it was stirred for 64 h. The reaction mixture was quenched with water (150 mL) and then concentrated in vacuo to remove tetrahydrofuran. The remaining residue was further diluted with water (100 mL) and then extracted with ethyl acetate (1×250 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 3/1 hexanes/ethyl acetate) afforded 2-(3,4-bis-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid methyl ester (1.61 g, 67%) as a yellow oil: EI-HRMS m/e calcd for C17H24O6S2 (M+) 388.1014, found 388.1014.

Workup

  1. customThe resulting reaction mixture
  2. customThe resulting reaction mixture
  3. stirringto stir at −78° C. for 1 h, at which time
  4. temperatureto warm to 25° C. where it
  5. stirringwas stirred for 64 h
  6. customThe reaction mixture was quenched with water (150 mL)
  7. concentrationconcentrated in vacuo
  8. customto remove tetrahydrofuran
  9. additionThe remaining residue was further diluted with water (100 mL)
  10. extractionextracted with ethyl acetate (1×250 mL)
  11. washThe organic layer was washed with a saturated aqueous sodium chloride solution (1×100 mL)
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c0a4691661c74decb0c56bf072da888f
Source dataset
uspto-grants-2001_11
Patent number
US06320050B1

Reaction notes

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