Diisopropylamine → Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

HRID 503820Notes

Reaction equation

HRID 503820 reaction equation
[CH2:1]([Li])CCC.[CH:6]([NH:9][CH:10]([CH3:12])C)(C)C.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[CH:27]1[CH:32]=[CH:31][C:30]([N:33](S(C(F)(F)F)(=O)=O)[S:34]([C:37]([F:40])([F:39])[F:38])(=[O:36])=[O:35])=[CH:29][CH:28]=1>C1COCC1.C(OCC)(=O)C>[CH:23]1([CH2:24][CH2:25][NH:20][C:18]([C:27]2[CH:32]=[CH:31][C:30]([C:29]3[CH2:28][CH2:6][NH:9][CH2:10][CH:12]=3)=[N:33][CH:1]=2)=[O:19])[CH2:22][CH2:21]1.[C:13]([O:17][C:18]([N:20]1[CH2:21][CH:22]=[C:23]([O:26][S:34]([C:37]([F:40])([F:39])[F:38])(=[O:36])=[O:35])[CH2:24][CH2:25]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 142176Phenyl triflimideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 2

HCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateYield 60%HCID 86617865HCID 86617865, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of n-butyllithium (18.8 mL, 30.113 mmol) in THF (40.0 mL) was added diisopropylamine (4.2 mL, 30.113 mmol) at −78° C. The resulting mixture was stirred at −78° C. for 10 minutes. 4-Oxo-piperidine-1-carboxylic acid tert-butyl ester (4.000 g, 20.075 mmol), dissolved in THF (40 mL), was added to the mixture and the whole was left stirring at −78° C. for another 30 minutes. N-Phenyltrifluoromethanesulfonimide was added to the mixture at −78° C. and the solution was warmed up to room temperature over 3 hours. Ethyl acetate (200 mL) was added to the mixture and the organic phase was washed with water (100 mL), brine (100 mL), dried over MgSO4 and then concentrated in vacuo. The crude product was purified by column chromatography, eluting with a solvent gradient of 20% ethyl acetate and 80% hexane to yield the desired product, 4-trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (4.000 g, 60%).

Workup

  1. additionwas added to the mixture
  2. waitthe whole was left
  3. stirringstirring at −78° C. for another 30 minutes
  4. temperaturethe solution was warmed up to room temperature over 3 hours
  5. washthe organic phase was washed with water (100 mL), brine (100 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography
  9. washeluting with a solvent gradient of 20% ethyl acetate and 80% hexane

Sources & evidence

ORD record
ord-1e4219ec64d84f24b140ba39e74d7bb1
Source dataset
uspto-grants-2010_08
Patent number
US07777036B2

Reaction notes

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