Isobutyric Acid → HCID 20286545, compound

HRID 1389463Notes

Reaction equation

HRID 1389463 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([OH:18])(=[O:17])[CH:14]([CH3:16])[CH3:15].[C:19]([N:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]1)([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>O1CCCC1.C(OCC)C>[C:19]([N:29]1[CH2:30][CH2:31][C:32]([C:14]([CH3:16])([CH3:15])[C:13]([OH:18])=[O:17])([OH:35])[CH2:33][CH2:34]1)([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]

Participants

7

Reactant 4

HCID 6590Isobutyric AcidHCID 7912DiisopropylamineHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 20286545HCID 20286545, compoundYield 51.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a 100 ml flask maintained under argon are added 2.22 g of diisopropylamine and 15 ml tetrahydrofuran. The contents of the flask are cooled to 0° and are maintained at that temperature. A solution of 1.5 M n-butyllithium (14.7 ml) is added and the solution is stirred for five minutes. Isobutyric acid (0.88 g) is added and the mixture is stirred for 15 minutes at 20°. The mixture is cooled to -70° and a solution of 2.33 g of N-carbobenzyloxy-4-piperidone in 5 ml tetrahydrofuran is added at such a rate that the temperature remains below -50°. The mixture is allowed to warm to room temperature and is poured into 150 ml diethyl ether. This solution is extracted with two 150 ml portions of 1 N hydrochloric acid, 50 ml of water, and 100 ml of 2% sodium hydroxide. The basic layer is acidified with 10 N hydrochloric acid and the resulting mixture is extracted with three 50 ml portions of diethyl ether. Evaporation of the ether affords an oil which is triturated with 50 ml hexane to give 1.65 g 2-(1-carbobenzyloxy-4-hydroxypiperidin-4-yl)-2-methylpropionic acid, an oil.

Workup

  1. temperatureTo a 100 ml flask maintained under argon
  2. temperatureThe contents of the flask are cooled to 0°
  3. temperatureare maintained at that temperature
  4. stirringthe mixture is stirred for 15 minutes at 20°
  5. temperatureThe mixture is cooled to -70°
  6. customremains below -50°
  7. extractionThis solution is extracted with two 150 ml portions of 1 N hydrochloric acid, 50 ml of water, and 100 ml of 2% sodium hydroxide
  8. extractionthe resulting mixture is extracted with three 50 ml portions of diethyl ether
  9. customEvaporation of the ether
  10. customaffords an oil which
  11. customis triturated with 50 ml hexane

Sources & evidence

ORD record
ord-caba64fef9c148f6b64fce10c7f032ac
Source dataset
uspto-grants-1981_01
Patent number
US04244961

Reaction notes

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