Water → methyl (2E)-3-{2-[(1R)-1-({(2R)-3-[(2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidin-1-yl]-2-hydroxypropyl}oxy)ethyl]phenyl}prop-2-enoate

HRID 1920782Notes

Reaction equation

HRID 1920782 reaction equation
[O:1]1[CH2:3][C@@H:2]1[CH2:4][O:5][C@@H:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1/[CH:14]=[CH:15]/[C:16]([O:18][CH3:19])=[O:17])[CH3:7].[F:20][C:21]1[CH:22]=[C:23]([CH:30]=[CH:31][C:32]=1[CH3:33])[CH2:24][C@@H:25]1[CH2:29][CH2:28][CH2:27][NH:26]1.Cl([O-])(=O)(=O)=O.[Li+].O>C1(C)C=CC=CC=1>[F:20][C:21]1[CH:22]=[C:23]([CH:30]=[CH:31][C:32]=1[CH3:33])[CH2:24][C@@H:25]1[CH2:29][CH2:28][CH2:27][N:26]1[CH2:3][C@@H:2]([OH:1])[CH2:4][O:5][C@@H:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1/[CH:14]=[CH:15]/[C:16]([O:18][CH3:19])=[O:17])[CH3:7]

Participants

6

Reactant 4

HCID 962WaterHCID 23665649Lithium perchlorateHCID 58580794(2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidineHCID 58662611methyl (2E)-3-(2-{(1R)-1-[(2R)-oxiran-2-yl methoxy]ethyl}phenyl)prop-2-enoate

Product 1

HCID 58580652methyl (2E)-3-{2-[(1R)-1-({(2R)-3-[(2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidin-1-yl]-2-hydroxypropyl}oxy)ethyl]phenyl}prop-2-enoateYield 61%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of methyl (2E)-3-(2-{(1R)-1-[(2R)-oxiran-2-yl methoxy]ethyl}phenyl)prop-2-enoate (237 mg, 0.90 mmol) described in WO 2004/106280, (2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidine (167 mg, 0.86 mmol), which had been obtained in Example 1 (1e), and lithium perchlorate (55 mg, 0.52 mmol) in toluene (9 mL) was stirred at room temperature for 16 hours. Water (10 mL) was added to the reaction solution, which was then extracted with ethyl acetate (10 mL×3). After that, the organic layers were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to give the title compound as a yellow oily substance (238 mg, yield 61%).

Workup

  1. extractionwas then extracted with ethyl acetate (10 mL×3)
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-1c414d5c743f4f8ab386096e8c995b44
Source dataset
uspto-grants-2012_05
Patent number
US08173631B2

Reaction notes

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