Diisopropylamine → HCID 59657499, compound

HRID 494159Notes

Reaction equation

HRID 494159 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([OH:20])(=[O:19])[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[O:21]=[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[CH2:24][CH2:23]1>C1COCC1>[CH2:31]([O:30][C:28]([N:25]1[CH2:26][CH2:27][C:22]([CH:14]([C:13]([OH:20])=[O:19])[CH2:15][CH2:16][CH2:17][CH3:18])([OH:21])[CH2:23][CH2:24]1)=[O:29])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 8892Hexanoic AcidHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 59657499HCID 59657499, compoundYield 99.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 15 mL (124 mmol) diisopropyl amine in 90 mL anhydrous THF at −40° C. was added dropwise 45 mL (113 mmol) of n-butyl lithium (2.5 M in hexanes) The reaction mixture was warmed to 0° C. A solution of 6.7 mL (62.1 mmol) hexanoic acid in 60 mL anhydrous THF was added dropwise. The reaction mixture stirred at −20° C. for an additional 20 m. The reaction mixture was cooled to −78° C. A solution of 15 g (64.3 mmol) benzyl 4-oxo-1-piperidine-carboxylate in 60 mL anhydrous THF was added dropwise. The reaction mixture slowly warmed to room temperature over 18 h. The reaction was quenched by addition of 25 mL of water. The mixture was acidified to pH 2 with 6N HCl. The aqueous layer was thrice extracted with EtOAc. The combined organic phase was dried over magnesium sulfate and evaporated under reduced pressure. Toluene was added to the light, yellow oil and evaporated under reduced pressure to provide 21.5 g (99%) of 4-(1-carboxy-pentyl)-4-hydroxy-piperidine-1-carboxylic acid benzyl ester: ms [M]+=350.

Workup

  1. temperatureThe reaction mixture was cooled to −78° C
  2. temperatureThe reaction mixture slowly warmed to room temperature over 18 h
  3. customThe reaction was quenched by addition of 25 mL of water
  4. extractionThe aqueous layer was thrice extracted with EtOAc
  5. dry with materialThe combined organic phase was dried over magnesium sulfate
  6. customevaporated under reduced pressure
  7. additionToluene was added to the light, yellow oil
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-45ec561995124108b607e7dd58bee1ae
Source dataset
uspto-grants-2009_05
Patent number
US07538122B2

Reaction notes

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