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

HRID 1751602Notes

Reaction equation

HRID 1751602 reaction equation
C[C@@:2]1([C:18]([O-:20])=[O:19])[CH2:6][C@:5](C)([C:7]([O-:9])=[O:8])[CH2:4][N:3]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[OH-].[Na+].Cl.[CH2:24]1COCC1>>[C:14]([O:13][C:11]([N:3]1[C@H:2]([C:18]([O:20][CH3:24])=[O:19])[CH2:6][C@H:5]([C:7]([OH:9])=[O:8])[CH2:4]1)=[O:12])([CH3:15])([CH3:16])[CH3:17]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 86688330(2S,4S)-1-tert-butyl 2,4-dimethylpyrrolidine-1,2,4-tricarboxylate

Product 1

HCID 69673205(3S,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidine-3-carboxylic acidYield 70%

Procedure

To a solution of (2S,4S)-1-tert-butyl 2,4-dimethylpyrrolidine-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-274d15110a2b491c976debc4f0634d17
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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