181869-54-5 → 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-ethoxycarbonyloxymethyl-1H-1,2,4-triazolium iodide

HRID 2186922Notes

Reaction equation

HRID 2186922 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:35])([CH2:29][N:30]1[CH:34]=[N:33][CH:32]=[N:31]1)[C@H:10]([N:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[N:26][N:25]=[N:24]3)=[CH:19][CH:18]=2)[C:13]1=[O:28])[CH3:11].[C:36](=[O:43])([O:40][CH2:41][I:42])[O:37][CH2:38][CH3:39]>C(#N)C>[I-:42].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:35])([C@H:10]([N:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[N:26][N:25]=[N:24]3)=[CH:19][CH:18]=2)[C:13]1=[O:28])[CH3:11])[CH2:29][NH+:30]1[CH2:34][N:33]([CH2:41][O:40][C:36]([O:37][CH2:38][CH3:39])=[O:43])[CH:32]=[N:31]1

Participants

4

Reactant 2

HCID 3002973181869-54-5HCID 22596764Ethyl iodomethyl carbonate

Product 1

HCID 699431041-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-ethoxycarbonyloxymethyl-1H-1,2,4-triazolium iodideYield 56.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-tetrazol-1-yl)phenyl]-2-imidazolidinone(1.31 g) and ethyl iodomethyl carbonate (1.25 g) was added acetonitrile (20 ml) and the mixture was stirred for 14 hours at 60° C. under an argon atmosphere. The reaction mixture was concentrated under reduced pressure and the residue was submitted to silica gel flush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=4/1). The fraction containing the desired compound was concentrated under reduced pressure. The residue was subjected to ODS column chromatography (eluent: methanol/water=3/2) to give 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-ethoxycarbonyloxymethyl-1H-1,2,4-triazolium iodide (Compound 17, 1.1 g) as a pale yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customflush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=4/1)
  3. additionThe fraction containing the desired compound
  4. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-4b3db0b0ff3b4729a525db04e9e274c3
Source dataset
uspto-grants-2002_06
Patent number
US06407129B1

Reaction notes

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