Lithium Hydroxide → 1-((Tert-butoxy)carbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid
Reaction equation
C[O:2][C:3]([CH:5]1[CH2:9][C:8]([F:11])([F:10])[CH2:7][N:6]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:4].[OH-].[Li+]>C(#N)C.O>[C:15]([O:14][C:12]([N:6]1[CH2:7][C:8]([F:10])([F:11])[CH2:9][CH:5]1[C:3]([OH:4])=[O:2])=[O:13])([CH3:18])([CH3:16])[CH3:17]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 25 °C
Procedure
4,4-Difluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (Example 14a, 7.53 g, 28.403 mmol) was dissolved in acetonitrile (330 mL) and a solution of lithium hydroxide (1.36 g, 56.807 mmol) in water (110 mL) was added. After stirring for 16 h at 25° C., the acetonitrile was removed in vacuo and the aqueous phase was slowly acidified with 1.0 M aqueous hydrochloric acid solution until a precipitate formed. The product was extracted into ethyl acetate (3×50 mL) and the combined organic layers were dried over sodium sulfate and filtered. The solvent was removed in vacuo to afford the desired product, 4,4-difluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.54 g, 6.13 mmol, 95.6% yield) as a brittle, tan solid, which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ: 1.51 (9H, s), 2.50-2.84 (2H, m), 3.71-3.90 (2H, m), 6.73 (1H, bs).
Workup
- customthe acetonitrile was removed in vacuo
- customformed
- extractionThe product was extracted into ethyl acetate (3×50 mL)
- dry with materialthe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- customThe solvent was removed in vacuo
Sources & evidence
- ORD record
- ord-6ec1ac666ea34450ae0be58e9e2e1427
- Source dataset
- uspto-grants-2008_12
- Patent number
- US07462611B2
Reaction notes
Loading…