Chloromethyl pivalate → 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-[(2,2-dimethylpropanoyloxy)methyl]-1H-1,2,4-triazolium chloride

HRID 1370615Notes

Reaction equation

HRID 1370615 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:42][CH2:43][Cl:44])(=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38]>CC(C)=O>[Cl-:44].[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]([CH2:43][O:42][C:36](=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38])[CH:32]=[N:31]1

Participants

4

Reactant 2

HCID 87885Chloromethyl pivalate2×HCID 3002973181869-54-5

Product 1

HCID 699426401-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-[(2,2-dimethylpropanoyloxy)methyl]-1H-1,2,4-triazolium chloride

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

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 (0.48 g) and acetone (10 ml) was added chloromethyl pivalate (2.9 ml), and the mixture was stirred under reflux. After 88 hours, chloromethyl pivalate (1.45 ml) was added to the mixture. The mixture was further stirred for 14 hours under reflux. The reaction mixture was concentrated under reduced pressure. To the residue was added diethyl ether (8 ml), and the resulting powder was collected by filtration. The powder 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-[(2,2-dimethylpropanoyloxy)methyl]-1H-1,2,4-triazolium chloride (Compound 2, 0.25 g) as a white powder.

Workup

  1. temperatureunder reflux
  2. stirringThe mixture was further stirred for 14 hours
  3. temperatureunder reflux
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additionTo the residue was added diethyl ether (8 ml)
  6. filtrationthe resulting powder was collected by filtration

Sources & evidence

ORD record
ord-c40565d095f442c1b53d8b22b9be1fc9
Source dataset
uspto-grants-2003_06
Patent number
US06583164B1

Reaction notes

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