(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → (2S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)N([O])C(C)(C)CCC1.OS([O-])(=O)=O.[K+]>C(OC(C)C)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[O:13])[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 2.5 °C
Procedure
A solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (1.0 eq.) in isopropyl acetate (5 vol) was cooled to 0° C. and TEMPO (0.05 eq.) was added. A solution of bleach (12.5 wt %, 1.2 eq., 2.6 vol) was then slowly added over 1 hour while maintaining the temperature at 0-5° C. The mixture was stirred and monitored by HPLC for completion, then aqueous 10% KHSO4 (2.5 vol) was added, stirred for 10 minutes, and then the phases were separated. The organic phase was washed with aqueous 5% Na2SO3 (2 vol) then brine (1 vol) then dried azeotropically and concentrated to afford the title compound as a solid. The solid was triturated with acetonitrile (1.0 vol) to remove residual color and impurities. 1H-NMR (400 MHz, DMSO): δ 4.54 (m, 1H), 3.82 (m, 1H), 3.67 (m, 1H); 3.15 (m, 1H); ≈2.50 (m, 1H, coincides with DMSO); 1.42 and 1.39 (2 s rotamers, 9H).
Workup
- additionA solution of bleach (12.5 wt %, 1.2 eq., 2.6 vol) was then slowly added over 1 hour
- stirringstirred for 10 minutes
- customthe phases were separated
- washThe organic phase was washed with aqueous 5% Na2SO3 (2 vol)
- dry with materialbrine (1 vol) then dried azeotropically
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-bed5c83237e6456d843bc684854a1f20
- Source dataset
- uspto-grants-2011_07
- Patent number
- US07985762B2
Reaction notes
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