(S)-benzyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate → (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][N:21](C(OCC3C=CC=CC=3)=O)[CH2:20][CH2:19]2)[C:14]1=[O:34]>C(O)C.Cl.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:14]1=[O:34]Participants
5
Reactant 1
Product 1
Reagents, catalysts & solvents 3
Procedure
A solution of (S)-benzyl 4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (1.3 g, 27 mmol) in ethanol (20 mL) and concentrated HCl (300 μL) was hydrogenated at 40 PSI with 10% Degussa type Pd/C (650 mg) for 18 hours. The mixture was filtered through celite and the solids were washed with MeOH (200 mL) and water (200 mL). The methanol in the filtrate was removed in vacuo. The water layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (600 mg, 1.7 mmol, 64%). Mass spectrum (apci) m/z=356.1 (M+H).
Workup
- filtrationThe mixture was filtered through celite
- washthe solids were washed with MeOH (200 mL) and water (200 mL)
- customThe methanol in the filtrate was removed in vacuo
- extractionThe water layer was extracted with EtOAc (3×100 mL)
- washThe combined organic layers were washed with brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-6cd014e48e554e738b3d989f84acb797
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08754226B2
Reaction notes
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