Sodium Acetate → 3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 1811339Notes

Reaction equation

HRID 1811339 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:14])[CH:6]([NH2:13])[C:7](=O)[C:8]([F:11])([F:10])[F:9])[CH3:3].C(OC([N:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][C:23]1=[O:29])=O)(C)(C)C.C([O-])(=O)C.[Na+]>O.O1CCOCC1>[CH2:2]([O:4][C:5]([C:6]1[NH:13][C:25]2[CH2:26][CH2:27][NH:22][C:23](=[O:29])[C:24]=2[C:7]=1[C:8]([F:11])([F:10])[F:9])=[O:14])[CH3:3]

Participants

6

Reactant 3

HCID 517045Sodium AcetateHCID 23730999tert-Butyl 2,4-dioxopiperidine-1-carboxylateHCID 866376902-Amino-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester hydrochloride

Product 1

HCID 666086723-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A stirred mixture of 2-amino-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester hydrochloride (7.54 g, 32 mmol), 2,4-dioxo-piperidine-1-carboxylic acid tert-butyl ester (6.2 g, 29.1 mmol) and sodium acetate (2.39 g, 29.1 mmol) in water (35 ml) and dioxane (35 ml) was heated to reflux for 2 hours. The mixture was cooled down to room temperature, and extracted with 15 to 1 solvent mixture of ethyl acetate and methanol (160 ml×3), the combined organic phase was washed with saturated sodium chloride, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure, the residue was purified by the silica gel column chromatography with dichloromethane:tetrahydrofuran:methanol (40:5:1) as eluents to give 3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (2.8 g, 35%) as a yellow solid.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 hours
  3. extractionextracted with 15 to 1 solvent mixture of ethyl acetate and methanol (160 ml×3)
  4. washthe combined organic phase was washed with saturated sodium chloride
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customthe residue was purified by the silica gel column chromatography with dichloromethane:tetrahydrofuran:methanol (40:5:1) as eluents

Sources & evidence

ORD record
ord-e40fd73d9315489e8b35ffc963919d0e
Source dataset
uspto-grants-2013_01
Patent number
US08362251B2

Reaction notes

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