Hydrochloric Acid → 1,2,4-Pyrrolidinetricarboxylic acid, 1-(1,1-dimethylethyl) 2,4-dimethyl ester, (2S,4S)-
Reaction equation
[C:1]([C@@H:3]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4]1)#N.Cl.[C:20](OC(OC(C)(C)C)=O)(OC(C)(C)C)=[O:21].C[OH:36]>>[N:6]1([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:7][C@@H:3]([C:1]([O:21][CH3:20])=[O:36])[CH2:4][C@H:5]1[C:15]([O:17][CH3:18])=[O:16]Participants
Reactant 4
Product 1
Procedure
To a solution of (2S,4S)-1-tert-butyl 2-methyl 4-cyanopyrrolidine-1,2-dicarboxylate (9.0 g, 35.4 mmol) in MeOH (196 mL) was added HCl (4M in 1,4-dioxane, 100 mL, 403 mmol). The solution was stirred at room temperature for 16 h and concentrated in vacuo. The crude intermediate was dissolved in EtOAc (180 mL) and basified with aqueous bicarbonate (sat.). Di-tert-butyl dicarbonate (8.5 g, 38.9 mmol) was added and the biphasic solution was stirred at room temperature for 12 h. The layers were then separated and the aqueous layer was back extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The crude oil was purified by silica gel chromatography (15% to 40% to 100% EtOAc/Hexanes) to provide (2S,4S)-1-tert-butyl 2,4-dimethyl pyrrolidine-1,2,4-tricarboxylate (9.56 g, 94%).
Workup
- concentrationconcentrated in vacuo
- dissolutionThe crude intermediate was dissolved in EtOAc (180 mL)
- stirringthe biphasic solution was stirred at room temperature for 12 h
- customThe layers were then separated
- extractionthe aqueous layer was back extracted with EtOAc
- washThe combined organic layers were washed with brine
- dry with materialdried over Na2SO4
- concentrationconcentrated
- customThe crude oil was purified by silica gel chromatography (15% to 40% to 100% EtOAc/Hexanes)
Sources & evidence
- ORD record
- ord-0ba95b49509f4b36987b1cf1aaf20ec6
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09233974B2
Reaction notes
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