Chloromethyl Methyl Ether → (2R, 4R)-(+)-2-(ethoxycarbonyl)-4-(methoxymethoxy)-1-(4-methoxyphenethyl)pyrrolidine

HRID 365330Notes

Reaction equation

HRID 365330 reaction equation
[CH2:1](Cl)[O:2][CH3:3].C(N(CC)C(C)C)(C)C.[CH2:14]([O:16][C:17]([C@H:19]1[CH2:23][C@@H:22]([OH:24])[CH2:21][N:20]1[CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1)=[O:18])[CH3:15]>ClCCl>[CH2:14]([O:16][C:17]([C@H:19]1[CH2:23][C@@H:22]([O:24][CH2:1][O:2][CH3:3])[CH2:21][N:20]1[CH2:25][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=1)=[O:18])[CH3:15]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 57269395(2R, 4R)-(+)-2-(ethoxycarbonyl)-4-hydroxy-1-(4-methoxy phenethyl) pyrrolidine

Product 1

HCID 57141110(2R, 4R)-(+)-2-(ethoxycarbonyl)-4-(methoxymethoxy)-1-(4-methoxyphenethyl)pyrrolidineYield 89.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

9.32 ml (123 mmol) of MOMCl was added to a solution of 25 ml (144 mmol) of N,N-diisopropylethylamine and 6.00 g (20.5mmol) of (2R, 4R)-(+)-2-(ethoxycarbonyl)-4-hydroxy-1-(4-methoxyphenethyl) pyrrolidine in dichloromethane (100 ml) and the mixture was stirred for 14 hours at room temperature. The mixture was washed with saturated aqueous sodium carbonate and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silicagel column chromatography (ethyl acetate:n-hexane=1:1) to give 6.20 g of (2R, 4R)-(+)-2-(ethoxycarbonyl)-4-(methoxymethoxy)-1-(4-methoxyphenethyl)pyrrolidine in 89.8% yield.

Workup

  1. washThe mixture was washed with saturated aqueous sodium carbonate and saturated aqueous sodium chloride
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silicagel column chromatography (ethyl acetate:n-hexane=1:1)

Sources & evidence

ORD record
ord-f1ca75b04b65408e959f154d5d70ebae
Source dataset
uspto-grants-2000_10
Patent number
US06127361

Reaction notes

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