Carbonic acid, 1-chloroethyl ethyl ester → 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-[1-(ethoxy-carbonyloxy)ethyl]-1H-1,2,4-triazolium chloride

HRID 1370619Notes

Reaction equation

HRID 1370619 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:44])([O:41][CH2:42][CH3:43])[O:37][CH:38]([Cl:40])[CH3:39]>C(#N)C>[Cl-:40].[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]([CH:38]([O:37][C:36]([O:41][CH2:42][CH3:43])=[O:44])[CH3:39])[CH:32]=[N:31]1

Participants

4

Reactant 2

HCID 162095Carbonic acid, 1-chloroethyl ethyl esterHCID 3002973181869-54-5

Product 1

HCID 699428981-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-[1-(ethoxy-carbonyloxy)ethyl]-1H-1,2,4-triazolium chlorideYield 1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °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 (0.61 g) and 1-chloroethyl ethyl carbonate (3.7 g) was added acetonitrile (1 ml), and the mixture was stirred for 38 hours at 95° 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 ODS column chromatography (eluent: methanol/water=3/2). The eluate was concentrated in vacuo. The residue was dissolved in water (10 ml), and lyophilized 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-[-1-(ethoxy-carbonyloxy)ethyl]-1H-1,2,4-triazolium chloride (Compound 7,90 mg) 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. concentrationThe eluate was concentrated in vacuo
  5. dissolutionThe residue was dissolved in water (10 ml)

Sources & evidence

ORD record
ord-6c7263f4118c47cb9f83a69d8a31030f
Source dataset
uspto-grants-2003_06
Patent number
US06583164B1

Reaction notes

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