HCID 3002971, compound → HCID 69942578, compound

HRID 1370627Notes

Reaction equation

HRID 1370627 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]=[CH: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][CH3:42])[O:37][CH2:38][Cl:39]>C(#N)C>[Cl-:39].[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:18]=[CH:19][C:20]([N:23]3[CH:27]=[CH:26][N:25]=[N:24]3)=[CH:21][CH:22]=2)[C:13]1=[O:28])[CH3:11])[CH2:29][NH+:30]1[CH2:34][N:33]([CH2:38][O:37][C:36]([O:40][CH2:41][CH3:42])=[O:43])[CH:32]=[N:31]1

Participants

4

Reactant 2

HCID 3002971HCID 3002971, compoundHCID 5325479Chloromethyl Ethyl Carbonate

Product 1

HCID 69942578HCID 69942578, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °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-1,2,3-triazol-1-yl)phenyl]-2-imidazolidinone(0.50 g) and chloromethyl ethyl carbonate (2.9 g) was added acetonitrile (0.5 ml), and the mixture was stirred for 22 hours at 100° C. The reaction mixture was concentrated under reduced pressure. To the residue was added diisopropyl ether (10 ml), and the resulting powder was collected by filtration. The powder was subjected to silica gel flush chromatography (eluent: ethyl acetate/acetone=1/1→acetone→acetone/ethanol=9/1→4/1), and the fraction containing the desired compound was concentrated under reduced pressure. The residue was subjected to ODS column chromatography (eluent: methanol/water=3/2). The eluate was concentrated in vacuo, and the residue was dissolved in water(15 ml). The solution was lyophilized to give 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1,2,3-triazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-ethoxycarbonyloxymethyl-1H-1,2,4-triazolium chloride (Compound 15, 0.14 g) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionTo the residue was added diisopropyl ether (10 ml)
  3. filtrationthe resulting powder was collected by filtration
  4. customflush chromatography (eluent: ethyl acetate/acetone=1/1→acetone→acetone/ethanol=9/1→4/1)
  5. additionthe fraction containing the desired compound
  6. concentrationwas concentrated under reduced pressure
  7. concentrationThe eluate was concentrated in vacuo
  8. dissolutionthe residue was dissolved in water(15 ml)

Sources & evidence

ORD record
ord-196793418c974e5986cd7241e77275b8
Source dataset
uspto-grants-2003_06
Patent number
US06583164B1

Reaction notes

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