Hydrochloric Acid → (2S,4S)-4-Hydroxy-1-(2-nitro-phenyl)-pyrrolidine-2-carboxylic Acid Methyl Ester

HRID 1697552Notes

Reaction equation

HRID 1697552 reaction equation
Cl.[CH3:2][O:3][C:4]([CH:6]1[CH2:10][CH:9]([OH:11])[CH2:8][NH:7]1)=[O:5].Cl[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20].Cl>C(#N)C>[CH3:2][O:3][C:4]([C@@H:6]1[CH2:10][C@H:9]([OH:11])[CH2:8][N:7]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20])=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 69451-Chloro-2-nitrobenzeneHCID 16242427Methyl 4-hydroxypyrrolidine-2-carboxylate hydrochloride

Product 1

HCID 12042756(2S,4S)-4-Hydroxy-1-(2-nitro-phenyl)-pyrrolidine-2-carboxylic Acid Methyl EsterYield 98.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 2S,4S)-4-hydroxy-pyrrolidine-2-carboxylic acid methyl ester hydrochloride (4.0 g, 1.0 eq) in acetonitrile (55 mL) was treated with TEA (3.8 g, 1.36 eq) and 1-chloro-2-nitrobenzene (4.1 g, 1.05 eq). A solution formed, followed by rapid formation of a white precipitate. The mixture was stirred at 60° C. for 22 h then poured over HCl 1N (60 mL) and extracted several times with ether. The combined organic extracts were dried over sodium sulfate and evaporated. Purification by flash chromatography on silica gel with an heptane/ethyl acetate gradient yielded the title compound as a white solid (5.8 g, 79%).

Workup

  1. customA solution formed
  2. extractionextracted several times with ether
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. customevaporated
  5. customPurification by flash chromatography on silica gel with an heptane/ethyl acetate gradient

Sources & evidence

ORD record
ord-f37f1098e83c43f68b1d60393fafb070
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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