Ethyl trifluoroacetate → tert-Butyl 3-oxo-4-(2,2,2-trifluoroacetyl)piperidine-1-carboxylate

HRID 1360164Notes

Reaction equation

HRID 1360164 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C[Si](C)(C)N[Si](C)(C)C.[Li].C([O:27][C:28](=O)[C:29]([F:32])([F:31])[F:30])C>C(COC)OC>[O:1]=[C:2]1[CH:7]([C:28](=[O:27])[C:29]([F:32])([F:31])[F:30])[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1

Participants

5

Reactant 3

HCID 9794Ethyl trifluoroacetateHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 57426343Lithium bis(trimethylsilyl)amide

Product 1

HCID 18456551tert-Butyl 3-oxo-4-(2,2,2-trifluoroacetyl)piperidine-1-carboxylateYield 81.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-78 °C

Procedure

5.0 g (25 mmol) of t-butyl 3-oxopiperidin-1-carboxylate was dissolved in dimethoxyethane, and the resulting solution was cooled to −78° C., then 30 mL (30 mmol) of lithium hexamethyldisilazane (LHMDS, 1M in THF) was dropwise added and stirred for about 1 hour, followed by dropwise addition of 3.9 mL (33 mmol) of ethyltrifluoroacetate. After stirring for 1 hour, a dryice/acetone bath was removed and then further stirred for about 2 hours and 30 minutes with the reaction solution being heated to room temperature. After the reaction solution was washed with a saturated aqueous ammonium chloride, extraction was conduced three times with ethyl acetate. An organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure, then the residue was purified by column chromatography (20:1 dichloromethane:methanol) to give 6.0 g of the title compound in a yield of 81%.

Workup

  1. stirringAfter stirring for 1 hour
  2. customa dryice/acetone bath was removed
  3. stirringfurther stirred for about 2 hours and 30 minutes with the reaction solution
  4. temperaturebeing heated to room temperature
  5. washAfter the reaction solution was washed with a saturated aqueous ammonium chloride, extraction
  6. dry with materialAn organic layer was dried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customthe residue was purified by column chromatography (20:1 dichloromethane:methanol)

Sources & evidence

ORD record
ord-05e5778ec4604448819d33748cc5aba6
Source dataset
uspto-grants-2011_02
Patent number
US07879848B2

Reaction notes

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