Hydrochloric Acid → N-(4,4-difluoropyrrolidin-3-yl)-3-(methylsulfonyl)propanamide hydrochloride
Reaction equation
[F:1][C:2]1([F:23])[CH:6]([NH:7][C:8](=[O:15])[CH2:9][CH2:10][S:11]([CH3:14])(=[O:13])=[O:12])[CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.[ClH:24]>C(#N)C.C(OCC)C>[ClH:24].[F:23][C:2]1([F:1])[CH2:3][NH:4][CH2:5][CH:6]1[NH:7][C:8](=[O:15])[CH2:9][CH2:10][S:11]([CH3:14])(=[O:13])=[O:12]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of tert-butyl 3,3-difluoro-4-{[3-(methylsulfonyl)propanoyl]amino}pyrrolidine-1-carboxylate (1.60 g, 4.5 mmol) in acetonitrile (45 mL) was added HCl (4 M in dioxane, 4.5 mL, 18 mmol, 4 mol eq). The resulting solution turned to a white suspension after 1 hr, and was stirred at ambient temperature for 3 hr. The volatiles were removed to dryness to give a white solid, which was suspended in ethyl ether (100 mL). The white solid was collected by filtration, washed with ether (20 mL) and dried to give the title product as a white solid (1.26 g, 96% yield, >95% purity, assumed 1 HCl salt). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.99 (br. s., 2 H) 8.75 (br. s., 1 H) 4.71-4.95 (m, 1 H) 3.58-3.89 (m, 3 H) 3.28-3.43 (m, 2 H) 3.16 (t, J=10.88 Hz, 2 H) 2.99 (s, 3 H) 2.67 (t, J=7.58 Hz, 2 H). 19F NMR (376 MHz, DMSO-d6) δ ppm −108.27-−107.26 (m, 1 F) −109.70-−108.82 (m, 1 F). m/z (APCI+) for C8H14F2N2O3S 257.2 (M+H)+.
Workup
- customThe volatiles were removed to dryness
- customto give a white solid, which
- filtrationThe white solid was collected by filtration
- washwashed with ether (20 mL)
- customdried
Sources & evidence
- ORD record
- ord-550a480965fe414fa652bdceedb288d2
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09290496B2
Reaction notes
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