Hydrochloric Acid → (2S,4S)-1-(tert-butoxycarbonyl)-4-((difluoromethoxy)methyl)pyrrolidine-2-carboxylic acid
Reaction equation
[F:1][CH:2]([F:21])[O:3][CH2:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:7]([C:17]([O:19]C)=[O:18])[CH2:6]1.[Li+].[OH-].Cl>C1COCC1.CO>[C:13]([O:12][C:10]([N:8]1[CH2:9][C@@H:5]([CH2:4][O:3][CH:2]([F:1])[F:21])[CH2:6][C@H:7]1[C:17]([OH:19])=[O:18])=[O:11])([CH3:16])([CH3:14])[CH3:15]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of (2S,4S)-1-tert-butyl 2-methyl 4-((difluoromethoxy)methyl)pyrrolidine-1,2-dicarboxylate (2.41 g, 7.79 mmol) in a mixture of THF (39 mL) and MeOH (15.6 mL) was added LiOH (2.5 M aqueous, 15.6 mL, 38.9 mmol). The resulting solution was stirred at room temperature for 1h. Upon completion by TLC the reaction mixture was acidified with aqueous HCl (1N). The desired product was extracted with CH2Cl2 (3×). The combined organic layers were dried over Na2SO4 and concentrated to provide (2S,4S)-1-(tert-butoxycarbonyl)-4-((difluoromethoxy)methyl)pyrrolidine-2-carboxylic acid (2.4 g, 99%). MS (ESI) m/z 294.96 [M −H]-. 1H-NMR: 400 MHz, (acetone-d6) δ (mixture of rotamers): 6.50 (t, 1H), 4.36-4.17 (m, 1H), 3.93 (d, 2H), 3.77-3.67 (m, 1H), 3.63-3.59 (m, 1H), 3.26-3.12 (m, 1H), 2.72-2.41 (m, 2H), 1.89-1.73 (m, 2H), 1.41 (s, 9H).
Workup
- extractionThe desired product was extracted with CH2Cl2 (3×)
- dry with materialThe combined organic layers were dried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-fe3a0881f4d04e56bc638fcb96c4e961
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221833B2
Reaction notes
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