Diisopropylamine → HCID 67483527, compound

HRID 1935232Notes

Reaction equation

HRID 1935232 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15](=[O:29])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1.I[CH2:31][CH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1>O1CCCC1.CN1CCCN(C)C1=O>[CH3:13][O:14][C:15](=[O:29])[CH:16]([C:17]1[CH:18]=[CH:19][C:20]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[CH:21][CH:22]=1)[CH2:31][CH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 2762531(Iodomethyl)cyclopentaneHCID 13703753(4-Morpholin-4-yl-phenyl)-acetic acid methyl esterHCID 178418339Butyllithium

Product 1

HCID 67483527HCID 67483527, compoundYield 51.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (344 μL, 2.45 mmol) in dry tetrahydrofuran (2.9 mL) was cooled to −78° C. under nitrogen and then treated with a 2.5M solution of n-butyllithium in hexanes (981 μL, 2.45 mmol). The reaction mixture was stirred at −78° C. for 15 min and then treated dropwise with a solution of (4-morpholin-4-yl-phenyl)-acetic acid methyl ester (549.9 mg, 2.34 mmol) in dry tetrahydrofuran (2 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 mL). The resulting reaction mixture was allowed to stir at −78° C. for 30 min, at which time, a solution of iodomethylcyclopentane (540.0 mg, 2.57 mmol) in a small amount of dry tetrahydrofuran was added dropwise. The reaction mixture was then allowed to warm to 25° C. where it was stirred for 67 h. The reaction mixture was quenched with water and then concentrated in vacuo to remove tetrahydrofuran. The aqueous residue was diluted with ethyl acetate (200 mL). The organic phase 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, 230-400 mesh, 3/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-morpholin-4-yl-phenyl)-propionic acid methyl ester (381.4 mg, 51%) as a white solid: mp 68-70° C.; EI-HRMS m/e calcd for C19H27NO3 (M+) 317.1991, found 317.2001.

Workup

  1. customThe resulting reaction mixture
  2. stirringto stir at −78° C. for 30 min, at which time
  3. temperatureto warm to 25° C. where it
  4. stirringwas stirred for 67 h
  5. customThe reaction mixture was quenched with water
  6. concentrationconcentrated in vacuo
  7. customto remove tetrahydrofuran
  8. additionThe aqueous residue was diluted with ethyl acetate (200 mL)
  9. washThe organic phase 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-b14e583026e94b359dd15085ff9d7bee
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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