Hydrochloric Acid → methyl 3-(S)-n-butyl-3-[2-(S)-carboxypyrrolidin-1-yl-carbonyl)-2-(S)-fluoropropionate
Reaction equation
[CH2:1]([C@@H:5]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]([O:21]C(C)(C)C)=[O:20])=[O:13])[C@H:6]([F:11])[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4].Cl>O1CCOCC1>[CH2:1]([C@@H:5]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]([OH:21])=[O:20])=[O:13])[C@H:6]([F:11])[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(S)-fluoropropionate H-4 (4.3 mmol) was added 4 N HCl in dioxane (15 mL), the solution stirred for 2 h, then evaporated to dryness to afford 4.3 mmol of methyl 3-(S)-n-butyl-3-[2-(S)-carboxypyrrolidin-1-yl-carbonyl)-2-(S)-fluoropropionate H-5 (quant.). To H-5 (0.15 mmol) in dioxane (1 mL) was added an amine (0.15 mmol), DIEA (0.38 mmol), and HATU or similar coupling reagent (0.15 mmol) and the solution stirred for 8 h. The reaction was cooled to 0° C., aqueous 50% hydroxylamine was added (0.5 mL) and the reaction stirred for 4 h. The crude reaction mixture was then purified by preparative reverse-phase (C18) HPLC to afford N-hydroxy-3-(S)-n-butyl-3-[2-(S)-aminocarbonylpyrrolidin-1-yl-carbonyl)-2-(S)-fluoropropionamide H-6.
Workup
- customevaporated to dryness
Sources & evidence
- ORD record
- ord-c7cb9b6c3d834b459fde4c306ce54958
- Source dataset
- uspto-grants-2004_09
- Patent number
- US06797820B2
Reaction notes
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