Hydrochloric Acid → (3R,4R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methyl-piperidine-1-carboxylate

HRID 1969592Notes

Reaction equation

HRID 1969592 reaction equation
[CH3:1][C@@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@@H:3]1[C:15]1[N:19]2[C:20]3[CH:26]=[CH:25][N:24](S(C4C=CC(C)=CC=4)(=O)=O)[C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1.[OH-].[Na+].Cl>O1CCOCC1>[C:15]1([C@@H:3]2[C@H:2]([CH3:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4]2)[N:19]2[C:20]3[CH:26]=[CH:25][NH:24][C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58557067(3R,4R)-tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

Product 1

HCID 58557258(3R,4R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methyl-piperidine-1-carboxylateYield 108.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (3R,4R)-tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (40 g, 78 mmol, Example #5 Step H) in 1,4-dioxane (160 mL) was added NaOH (1 N aqueous, 157 mL). The reaction was heated at about 60° C. for about 1 h. The reaction was allowed to cool to ambient temperature. The reaction was neutralized with aqueous HCl (4 N, 50 mL). The layers and extracted with DCM (2×300 mL). The combined organic extracts were washed with brine (400 mL), dried over anhydrous Na2SO4, filtered then concd in vacuo. The product was purified by chromatography on silica gel (330 g) using 1-5% MeOH in DCM to give (3R,4R)-tert-butyl 3-(6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-methylpiperidine-1-carboxylate (30 g, 99%): LC/MS (Table 1, Method b) Rt=2.00 min; MS m/z: 356 (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionThe layers and extracted with DCM (2×300 mL)
  3. washThe combined organic extracts were washed with brine (400 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customThe product was purified by chromatography on silica gel (330 g)

Sources & evidence

ORD record
ord-555d03b05a4647b38f597d0caad4f856
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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