Methanol → Trans-4-(3-bromophenyl)-1-Boc-pyrrolidine-3-carboxylic acid

HRID 1524287Notes

Reaction equation

HRID 1524287 reaction equation
[OH-].[Li+].C[O:4][C:5]([C@H:7]1[C@H:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=2)[CH2:10][N:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:8]1)=[O:6].CO.O1CCCC1>O>[C:22]([O:21][C:19]([N:9]1[CH2:10][C@@H:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=2)[C@H:7]([C:5]([OH:6])=[O:4])[CH2:8]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 86667842rac-1-tert-butyl 3-methyl (3R,4S)-4-(3-bromophenyl)pyrrolidine-1,3-dicarboxylate

Product 1

HCID 2762118Trans-4-(3-bromophenyl)-1-Boc-pyrrolidine-3-carboxylic acidYield 68.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Add lithium hydroxide (0.50 g, 12 mmol) to a solution of trans-4-(3-bromo-phenyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (0.80 g, 2.08 mmol) in a 1:2:1 mixture of MeOH:tetrahydrofuran:water (8 mL). Stir the mixture at room temperature for 3 h then concentrate under reduced pressure to remove volatile organics. Wash the concentrated aqueous mixture with EtOAc and then acidify to pH 5 using a 0.5 M solution of citric acid. Extract the mixture with EtOAc, dry over anhydrous sodium sulfate, and concentrate under reduced pressure to provide 0.53 g of trans-4-(3-bromo-phenyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester.

Workup

  1. concentrationthen concentrate under reduced pressure
  2. customto remove volatile organics
  3. washWash the concentrated aqueous mixture with EtOAc
  4. extractionExtract the mixture with EtOAc
  5. dry with materialdry over anhydrous sodium sulfate
  6. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-6dbb5b3538c0448585894ca832f847cd
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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