Hydrochloric Acid → (S)-3-(1H-indazol-5-yloxy)-1-(piperidin-4-yl)pyrrolidin-2-one

HRID 407967Notes

Reaction equation

HRID 407967 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C@H:11]3[CH2:15][CH2:14][N:13]([CH:16]4[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]4)[C:12]3=[O:29])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.Cl.O1CCOCC1.CO>C(Cl)Cl.C(OCC)(=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C@H:11]3[CH2:15][CH2:14][N:13]([CH:16]4[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]4)[C:12]3=[O:29])=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887Methanol3×HCID 312751,4-DioxaneHCID 67470553(S)-tert-butyl 4-(3-(1H-indazol-5-yloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

Product 1

HCID 67470590(S)-3-(1H-indazol-5-yloxy)-1-(piperidin-4-yl)pyrrolidin-2-oneYield 100%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with (S)-tert-butyl 4-(3-(1H-indazol-5-yloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (0.300 g, 0.749 mmol), HCl in dioxane (1.87 mL, 7.49 mmol), DCM (10 mL), and methanol (1 mL). The reaction was stirred at ambient temperature for 2 hours. The organic solvents were removed under reduced pressure. The residue was purified using silica gel column chromatography using 50-100% ethyl acetate in hexanes, then 5% ammoniated methanol in DCM, and then 30% ammoniated methanol in ethyl acetate to provide (S)-3-(1H-indazol-5-yloxy)-1-(piperidin-4-yl)pyrrolidin-2-one (0.225 g, 100% yield).

Workup

  1. customThe organic solvents were removed under reduced pressure
  2. customThe residue was purified

Sources & evidence

ORD record
ord-47e4827156ac4c648de3d796ee6a0db0
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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