Triethylamine → (2S,4R)-1-(3-Chloro-benzyl)-4-hydroxy-pyrrolidine-2-carboxylic acid methyl ester

HRID 490638Notes

Reaction equation

HRID 490638 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8]Cl)[CH:3]=1.Cl.[CH3:11][O:12][C:13]([CH:15]1[CH2:19][CH:18]([OH:20])[CH2:17][NH:16]1)=[O:14].C(N(CC)CC)C.[OH-].[Na+]>ClCCl>[CH3:11][O:12][C:13]([C@@H:15]1[CH2:19][C@@H:18]([OH:20])[CH2:17][N:16]1[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)=[O:14]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12103m,alpha-DichlorotolueneHCID 14798Sodium HydroxideHCID 16242427Methyl 4-hydroxypyrrolidine-2-carboxylate hydrochloride

Product 1

HCID 67547981(2S,4R)-1-(3-Chloro-benzyl)-4-hydroxy-pyrrolidine-2-carboxylic acid methyl esterYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Chloro-3-chloromethyl-benzene (15.2 ml, 120 mmol) was added to the mixture of 4-hydroxy-pyrrolidine-2-carboxylic acid methyl ester hydrochloride (14.5 g, 80 mmol) and triethylamine (18.6 g, 180 mmol) in dichloromethane (120 ml). The reaction mixture was refluxed overnight. After cooling, 1M aqueous sodium hydroxide was added, and the mixture was extracted with dichloromethane. The extract was washed with brine, dried over sodium sulfate, concentrated and purified by chromatography on silica gel (hex/EA=5:1 to hex/EA=31) to give 14 g title product as yellow oil in 65% yield.

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with dichloromethane
  4. washThe extract was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by chromatography on silica gel (hex/EA=5:1 to hex/EA=31)

Sources & evidence

ORD record
ord-f27d9208470e4f46be0005abcc66cb8d
Source dataset
uspto-grants-2009_05
Patent number
US07528136B2

Reaction notes

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