Pyridine → methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-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:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:13])[C@@H:6](O)[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4].N1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)[F:36])(=O)=O.[O-]S(C(F)(F)F)(=O)=O>C(Cl)Cl>[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:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:13])[C@H:6]([F:36])[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -20 °C
Procedure
To methyl 3-(R)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(R)-hydroxypropionate H-3 (8.7 mmol) in DCM (10 mL) was added pyridine (25 mmol), the reaction was cooled to −20° C., then triflic anhydride (12.5 mmol) was added. The solution was stirred for 1 hour, then worked up as described above. The intermediate triflate was resuspended in DCM and cooled to −50° C. Tris(dimethylamino)sulfur (trimethylsilyl)difluoride (TAS-F) was added (8.7 mmol) and the solution allowed to warm to rt. The reaction mixture was washed with aqueous sodium bicarbonate and brine, dried (Na2SO4) and concentrated, then purified on silica gel (ethylacetate/hexanes) to afford 4.3 mmol (50%) of methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-yl-carbonyl)-2-(S)-fluoropropionate H-4.
Workup
- temperaturecooled to −50° C
- temperatureto warm to rt
- washThe reaction mixture was washed with aqueous sodium bicarbonate and brine
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- custompurified on silica gel (ethylacetate/hexanes)
Sources & evidence
- ORD record
- ord-4ae3a06c71884e0fb8e0674ac450b597
- Source dataset
- uspto-grants-2004_09
- Patent number
- US06797820B2
Reaction notes
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