Ethyl Acetate → (R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

HRID 1969783Notes

Reaction equation

HRID 1969783 reaction equation
S([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24]4)=[N:21][CH:22]=3)[C:14]=2[CH:13]=[CH:12]1)(C1C=CC(C)=CC=1)(=O)=O.[OH-].[Na+].CCOC(C)=O.[NH4+].[Cl-]>O1CCOCC1>[C:20]1([C@@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24]2)[N:19]2[C:14]3[CH:13]=[CH:12][NH:11][C:15]=3[N:16]=[CH:17][C:18]2=[CH:22][N:21]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 58557605(R)-tert-butyl 3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

Product 1

HCID 58557937(R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-tert-butyl 3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (4.44 g, 8.96 mmol) in 1,4-dioxane (54 mL) was added NaOH (2 N aqueous, 8.9 mL, 18 mmol), and the resulting mixture was heated at about 60° C. for about 3 h. The reaction was cooled to ambient temperature and EtOAc (30 mL) and saturated aqueous NH4Cl (20 mL) were added. The organic layer was separated and the aqueous layer was further extracted with EtOAc (40 mL). The combined organic layers were washed with brine (40 mL), dried over anhydrous MgSO4, filtered, and coned under reduced pressure. The material was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM to afford (R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (2.80 g, 92%): LC/MS (Table 1, Method b) Rt=1.85 min; MS m/z: 342 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was further extracted with EtOAc (40 mL)
  4. washThe combined organic layers were washed with brine (40 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customThe material was purified by silica gel chromatography
  8. washeluting with a gradient of 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-bc542c2f3f494220afe3eec2b5fc720d
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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