Diisopropylamine → 1-(4-Pyridylmethyl)cyclopentanecarboxylic Acid

HRID 54231

Reaction equation

HRID 54231 reaction equation
[H-].[Na+].C(NC(C)C)(C)C.[CH:10]1([C:15]([OH:17])=[O:16])[CH2:14][CH2:13][CH2:12][CH2:11]1.C([Li])CCC.Cl[CH2:24][C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1.Cl.ClCC1C=CN=CC=1.C(=O)(O)[O-].[Na+].[OH-].[Na+]>O1CCCC1.CCCCCC>[N:28]1[CH:29]=[CH:30][C:25]([CH2:24][C:10]2([C:15]([OH:17])=[O:16])[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:26][CH:27]=1

Participants

11

Reactant 8

HCID 7912DiisopropylamineHCID 14798Sodium HydroxideHCID 18840Cyclopentanecarboxylic acidHCID 24758Sodium hydrideHCID 745704-(Chloromethyl)pyridinium chlorideHCID 745714-(Chloromethyl)pyridineHCID 516892Sodium BicarbonateHCID 178418339Butyllithium

Product 1

HCID 214654951-(4-Pyridylmethyl)cyclopentanecarboxylic AcidYield 24.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of 3.69 g (123 mmol) of 80% sodium hydride in 150 mL of anhydrous tetrahydrofuran and 11.6 g (115 mmol) of diisopropylamine, at 0° C. was added 12.82 g (112 mmol) of cyclopentanecarboxylic acid. This was then heated at reflux for 15 minutes, cooled to 0° C. and 45 mL of 2.5M n-butyllithium in hexane added. After 15 minutes at 0° C. and 30 minutes at 35° C., the mixture was recooled to 0° C. and a solution of 14.4 g (112 mmol) of 4-chloromethylpyridine (freshly prepared from 4-chloromethylpyridine hydrochloride by neutralization with aqueous sodium bicarbonate, extraction with hexane, drying and concentrating) was added. After 30 minutes at 0° C. and 60 minutes at 35° C., the mixture was cooled to 0° C., water carefully added and extracted twice with diethyl ether. The aqueous layer was acidified to pH 3 with 6N hydrochloric acid whereupon a precipitate formed. The pH was adjusted to 5.9 with 10% sodium hydroxide and the solids collected. Recrystallization from hot ethanol and hexane afforded 5.7 g of desired product, m/e 206 (M+H).

Workup

  1. temperatureThis was then heated
  2. temperatureat reflux for 15 minutes
  3. custom30 minutes
  4. customat 35° C.
  5. customwas recooled to 0° C.
  6. customdrying
  7. concentrationconcentrating)
  8. additionwas added
  9. waitAfter 30 minutes at 0° C.
  10. temperature60 minutes at 35° C., the mixture was cooled to 0° C.
  11. additionwater carefully added
  12. extractionextracted twice with diethyl ether
  13. customformed
  14. customthe solids collected
  15. customRecrystallization from hot ethanol and hexane

Sources & evidence

ORD record
ord-dbfb7c6cc6e24ebd87108662e016b77e
Source dataset
uspto-grants-1997_04
Patent number
US05622949

Linked notes

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