Diisopropylamine → HCID 22315105, compound

HRID 430206Notes

Reaction equation

HRID 430206 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]([F:27])([F:26])[S:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=[O:24])=[CH:18][CH:17]=1.I[CH2:29][CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>O1CCCC1.CN1CCCN(C)C1=O>[CH:30]1([CH2:29][CH:22]([C:19]2[CH:18]=[CH:17][C:16]([S:15][C:14]([F:26])([F:13])[F:27])=[CH:21][CH:20]=2)[C:23]([OH:25])=[O:24])[CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 2762531(Iodomethyl)cyclopentaneHCID 27779024-(Trifluoromethylthio)phenylacetic acidHCID 178418339Butyllithium

Product 1

HCID 22315105HCID 22315105, compoundYield 58%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (2.4 mL, 16.80 mmol) in dry tetrahydrofuran (7.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2.5 mL) was cooled to −78° C. under nitrogen and then treated with a 2.5M solution of n-butyllithium in hexanes (6.7 mL, 16.80 mmol). The resulting reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of 4-(trifluoromethylthio)phenylacetic acid (1.89 g, 8.00 mmol) in dry tetrahydrofuran (7.5 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone (2.5 mL). The reaction mixture was allowed to stir at −78° C. for 55 min, at which time, a solution of iodomethylcyclopentane (1.85 g, 8.80 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 41 h. The reaction mixture was quenched with water and then concentrated in vacuo to remove tetrahydrofuran. The remaining aqueous phase was acidified to pH=2 with a 10% aqueous hydrochloric acid solution and then extracted with ethyl acetate (1×300 mL). The organic layer was washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 3/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-trifluoromethylsulfanyl-phenyl)propionic acid (1.47 g, 58%) as a cream solid: mp 69-71° C.; EI-HRMS m/e calcd for C15H17F3O2S (M+) 318.0901, found 318.0912.

Workup

  1. customThe resulting reaction mixture
  2. stirringto stir at −78° C. for 55 min, at which time
  3. temperatureto warm to 25° C. where it
  4. stirringwas stirred for 41 h
  5. customThe reaction mixture was quenched with water
  6. concentrationconcentrated in vacuo
  7. customto remove tetrahydrofuran
  8. extractionextracted with ethyl acetate (1×300 mL)
  9. washThe organic layer was washed with a saturated aqueous sodium chloride solution (1×100 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-becf2b6dd049459e8434f473cecfd0ae
Source dataset
uspto-grants-2001_11
Patent number
US06320050B1

Reaction notes

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