Cesium carbonate → tert-Butyl (3S)-3-(4-quinolylamino)pyrrolidine-1-carboxylate

HRID 333938Notes

Reaction equation

HRID 333938 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[NH2:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]1.Cl[C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=[CH:23][CH:22]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:21]([NH:7][C@H:8]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 691404-ChloroquinolineHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidine

Product 1

HCID 86691593tert-Butyl (3S)-3-(4-quinolylamino)pyrrolidine-1-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

A 5 ml vial was charged with Cs2CO3 (654 mg, 3.3 mmol) and was dried in vacuo at 60° C. for two hours. Palladium acetate (31.5 mg, 0.14 mmol), BI NAP (43 mg, 0.07 mmol) were added followed by anhydrous dioxane (2 ml). The mixture was sonicated for one hour after which tert-butyl (3R)-3-aminopyrrolidine-1-carboxylate (186.3 mg, 1.0 mmol) and 4-chloroquinoline (163 mg, 1 mmol) dissolved in 2 ml anhydrous dioxane were added. The mixture was stirred at 100° C. overnight. The reaction mixture was purified directly by column chromatography (prepacked silica column, gradient heptan/ethyl acetate). 231 mg (0.68 mmol, 68%) of a solid were obtained. MS (APCI): m/z=314.0 [M+1]+.

Workup

  1. customwas dried in vacuo at 60° C. for two hours
  2. additionwere added
  3. customThe reaction mixture was purified directly by column chromatography (prepacked silica column, gradient heptan/ethyl acetate)

Sources & evidence

ORD record
ord-a24aa5fe9eaa4b65af6674a29b9e4e5d
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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