Hydrochloric Acid → (3S,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidine-3-carboxylic acid

HRID 1412928Notes

Reaction equation

HRID 1412928 reaction equation
[N:1]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C@@H:4]([C:6]([O:8]C)=[O:7])[CH2:3][C@H:2]1[C:10]([O:12][CH3:13])=[O:11].[OH-].[Na+].Cl>C1COCC1>[C:17]([O:16][C:14]([N:1]1[C@H:2]([C:10]([O:12][CH3:13])=[O:11])[CH2:3][C@H:4]([C:6]([OH:8])=[O:7])[CH2:5]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 108508301,2,4-Pyrrolidinetricarboxylic acid, 1-(1,1-dimethylethyl) 2,4-dimethyl ester, (2S,4S)-

Product 1

HCID 69673205(3S,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidine-3-carboxylic acidYield 70.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,4S)-1-tert-butyl 2,4-dimethyl pyrrolidine-1,2,4-tricarboxylate (9.56 g, 33.3 mmol) in THF (70 mL) at 0° C. (external temperature, ice bath) was added NaOH (1N aqueous, 33 mL, 33.3 mmol) dropwise over 15 min. The solution was stirred at 0° C. for 5 h before acidification with HCl (1N). The solution was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by silica gel chromatography (2% to 5% to 10% MeOH/CH2Cl2) to provide (3S,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidine-3-carboxylic acid (6.38 g, 70%).

Workup

  1. extractionThe solution was extracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude oil was purified by silica gel chromatography (2% to 5% to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-4608fe2c5d2844ccbb702d2d9ba02836
Source dataset
uspto-grants-2014_12
Patent number
US08921341B2

Reaction notes

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