Ethyl Acetate → tert-Butyl 4-(3-oxobutanoyl)piperidine-1-carboxylate

HRID 1245592Notes

Reaction equation

HRID 1245592 reaction equation
[C:1]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[C:17](OCC)(=[O:19])[CH3:18].CC(C)([O-])C.[K+]>CC(OC)(C)C>[C:13]([O:12][C:10]([N:7]1[CH2:6][CH2:5][CH:4]([C:1](=[O:3])[CH2:2][C:17](=[O:19])[CH3:18])[CH2:9][CH2:8]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 109879834-Acetyl-piperidine-1-carboxylic acid tert-butyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 21912749tert-Butyl 4-(3-oxobutanoyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

A solution of 2.27 g (10.0 mmol) of 4-acetyl-1-(tert-butoxycarbonyl)piperidine (from Step A), 1.95 mL (20.0 mmol) of ethyl acetate and 2.24 g (20.0 mmol) of potassium t-butoxide in 25 mL of MTBE was stirred at rt for 20 h. The reaction was quenched with 50 mL of 0.5 N KHSO4 and extracted with 150 mL of ether. The extract was dried over MgSO4 and concentrated. Flash chromatography on 70 g of silica gel using 20:1 v/v hexanes/acetone as the eluant afforded the title compound. The enol form predominated in CDCl3 solution: 1H NMR (500 MHz, CDCl3) δ 1.46 (s, 9H), 1.53 (dq, J=4.5, 12.5, 2H), 1.81 (app d, J=13.5, 2h), 2.07 (s, 3H), 2.44–2.33 (m, 1H), 2.72–2.79 (m, 2H), 4.18–4.28 (br s, 2H), 5.50 (s, 1H).

Workup

  1. customThe reaction was quenched with 50 mL of 0.5 N KHSO4
  2. extractionextracted with 150 mL of ether
  3. dry with materialThe extract was dried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-61b71d9c0b3c4d12a9efddfd458c6a5a
Source dataset
uspto-grants-2006_10
Patent number
US07125887B2

Reaction notes

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