1,8-Diazabicyclo(5.4.0)undec-7-ene → (S)-tert-Butyl 2-(3-(4-(1-methylpiperidin-4-yl)piperazin-1-ylsulfonyl)propyl)pyrrolidine-1-carboxylate

HRID 1643454Notes

Reaction equation

HRID 1643454 reaction equation
FC1C(F)=C(F)C(F)=C(F)C=1O[S:5]([CH2:8][CH2:9][CH2:10][C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])(=[O:7])=[O:6].[CH3:31][N:32]1[CH2:37][CH2:36][CH:35]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH2:34][CH2:33]1.N12CCCN=C1CCCCC2.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:31][N:32]1[CH2:33][CH2:34][CH:35]([N:38]2[CH2:43][CH2:42][N:41]([S:5]([CH2:8][CH2:9][CH2:10][C@@H:11]3[CH2:15][CH2:14][CH2:13][N:12]3[C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])(=[O:6])=[O:7])[CH2:40][CH2:39]2)[CH2:36][CH2:37]1

Participants

7

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 5663241-(1-Methyl-4-piperidinyl)piperazineHCID 59367744(S)-tert-Butyl 2-(3-(perfluorophenoxysulfonyl)propyl)pyrrolidine-1-carboxylate

Product 1

HCID 59367787(S)-tert-Butyl 2-(3-(4-(1-methylpiperidin-4-yl)piperazin-1-ylsulfonyl)propyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-tert-Butyl 2-(3-(perfluorophenoxysulfonyl)propyl)pyrrolidine-1-carboxylate (2.8 g, 6.099 mmol) and 1-(1-methylpiperidin-4-yl)piperazine (1.676 g, 9.148 mmol) were dissolved in tetrahydrofuran (40 ml), 1,8-diazabicyclo[5.4.0]undec-7-ene (2.7 ml, 18.297 mmol) was added under an inert gas and the mixture was refluxed for 2 h. Ethyl acetate and saturated sodium bicarbonate solution (50 ml of each) were added, the phases were separated and the aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic phases were washed with saturated sodium bicarbonate solution (40 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with ethyl acetate/methanol/methylene chloride/ammonia (25% aq) (300:100:50:1). Yield: quantitative

Workup

  1. temperaturethe mixture was refluxed for 2 h
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (2×50 ml)
  4. washThe combined organic phases were washed with saturated sodium bicarbonate solution (40 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (silica gel) with ethyl acetate/methanol/methylene chloride/ammonia (25% aq) (300:100:50:1)

Sources & evidence

ORD record
ord-f335ffbf78ea4132a94ad5ff78a9dd92
Source dataset
uspto-grants-2012_02
Patent number
US08119805B2

Reaction notes

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