Hydrochloric Acid → Tert-butyl 4-(3-oxo-4-phenylbutanoyl)piperidine-1-carboxylate

HRID 1862641Notes

Reaction equation

HRID 1862641 reaction equation
[H-].[Na+].[C:3]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)(=[O:5])[CH3:4].[C:19]1([CH2:25][C:26](OC)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Cl>C1COCC1.CCOCC>[C:15]([O:14][C:12]([N:9]1[CH2:8][CH2:7][CH:6]([C:3](=[O:5])[CH2:4][C:26](=[O:27])[CH2:25][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][CH2:10]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7559Methyl phenylacetateHCID 24758Sodium hydrideHCID 109879834-Acetyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 18187492Tert-butyl 4-(3-oxo-4-phenylbutanoyl)piperidine-1-carboxylateYield 65.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 60% sodium hydride (1.07 g) in THF (15 mL) at 0° C. was added a solution of 4-acetyl-1-(t-butoxycarbonyl)piperidine from Step B2 (3.03g, 13.3 mmol) and methyl phenylacetate (6.01 g, 39.9 mmol) in THF (6 mL) over 20 min. The reaction was stirred for another 4 h as it was allowed to warm to rt. The mixture was diluted with ether (30 mL) and poured into 1N HCl. The layers were separated and the aqueous layer was extracted three times with ether. The combined organic layers were washed with brine (150 mL), dried over sodium sulfate and concentrated. The crude product was purified by FC (20% ethyl acetate in hexanes) to give the title compound (3.02 g). Rf: 0.30 (20% ethyl acetate in hexane). The 1H NMR data was the same as that obtained from the product of Method A.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted three times with ether
  3. washThe combined organic layers were washed with brine (150 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by FC (20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-198c25262dd643bbb233ad8e2946fd3c
Source dataset
uspto-grants-2003_03
Patent number
US06538002B1

Reaction notes

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