Diisopropylamine → 2-(1-Benzyl-4-hydroxypiperidin-4-yl)acetic acid

HRID 127256Notes

Reaction equation

HRID 127256 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[OH-:27].[Na+].[O:29]1[CH2:33][CH2:32]CC1>C(O)(=O)C>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([CH2:32][C:33]([OH:29])=[O:27])([OH:26])[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 178418339Butyllithium

Product 1

HCID 202864672-(1-Benzyl-4-hydroxypiperidin-4-yl)acetic acid

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 2.12 g diisopropylamine and 15 ml tetrahydrofuran is stirred under argon at 0°. To this solution is added over two minutes 14 ml of 1.5 M n-butyllithium. To this solution at 0° is added 0.6 g acetic acid. The mixture is stirred five minutes at 20° and then cooled to -70°. To this mixture is added a solution of 1.89 g N-benzyl-4-piperidone in 4 ml tetrahydrofuran. The mixture is allowed to warm to room temperature and poured into 50 ml 1% sodium hydroxide. This mixture is extracted with three 50 ml portions of diethyl ether. The aqueous phase is adjusted to pH 7.0 with 3 N hydrochloric acid and is extracted with five 40 ml portions of dichloromethane. Evaporation of the dichloromethane affords (1-benzyl-4-hydroxypiperidin-4-yl)acetic acid.

Workup

  1. stirringThe mixture is stirred five minutes at 20°
  2. temperaturecooled to -70°
  3. extractionThis mixture is extracted with three 50 ml portions of diethyl ether
  4. extractionis extracted with five 40 ml portions of dichloromethane
  5. customEvaporation of the dichloromethane

Sources & evidence

ORD record
ord-9b8fe024c27f4dd9bc896b5703f13cd9
Source dataset
uspto-grants-1981_03
Patent number
US04255432

Reaction notes

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