N-Boc-4,4-difluoro-L-proline methyl ester → (2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid
Reaction equation
[F:1][C:2]1([F:18])[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16]C)=[O:15])[CH2:3]1>CO.O1CCCC1.[OH-].[Na+]>[C:10]([O:9][C:7]([N:5]1[CH2:6][C:2]([F:1])([F:18])[CH2:3][C@H:4]1[C:14]([OH:16])=[O:15])=[O:8])([CH3:13])([CH3:11])[CH3:12]Participants
5
Procedure
1.08 g (4.08 mmol) of (S)-1-tert-butyl 2-methyl 4,4-difluoropyrrolidine-1,2-dicarboxylate (purchased from Aldrich®; cat. no. 702463) were dissolved in a mixture of 10 mL of methanol and 10 mL of tetrahydrofurane and 6.12 mL of a 2M aqueous solution of sodium hydroxide were added. The solution was stirred at room temperature for 1 hour and then the organic solvents were removed. The remaining solution was diluted with water and 6.12 mL of 2M hydrochloric acid were added. The product that precipitated was extracted with dichloromethane (×3), the combined organic layers were washed with brine, dried over magnesium sulphate, filtered and the solvent was removed. 1.01 g (99% yield) of the title compound were obtained as a white solid.
Workup
- additionwere added
- customthe organic solvents were removed
- additionThe remaining solution was diluted with water and 6.12 mL of 2M hydrochloric acid
- additionwere added
- customThe product that precipitated
- extractionwas extracted with dichloromethane (×3)
- washthe combined organic layers were washed with brine
- dry with materialdried over magnesium sulphate
- filtrationfiltered
- customthe solvent was removed
Sources & evidence
- ORD record
- ord-429dd18a78c443ad8a13d8876b6badf6
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340547B2
Reaction notes
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