Chloromethyl propionate → HCID 69944018, compound

HRID 1370625Notes

Reaction equation

HRID 1370625 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:40][CH2:41][Cl:42])(=[O:39])[CH2:37][CH3:38]>C(#N)C>[Cl-: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: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]([CH2:41][O:40][C:36](=[O:39])[CH2:37][CH3:38])[CH:32]=[N:31]1

Participants

4

Reactant 2

HCID 221144Chloromethyl propionateHCID 3002971HCID 3002971, compound

Product 1

HCID 69944018HCID 69944018, compoundYield 10.9%

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 (0.80 g) and chloromethyl propanate (4.07 g) was added acetonitrile (1.6 ml), and the mixture was stirred for 12 hours at 100° C. under an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and to the residue was added diisopropyl ether (8 ml). The resulting powder was collected by filtration. The powder was subjected to silica gel flush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=9/1→4/1), and a 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 (10 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-propanoyloxymethyl-1H-1,2,4-triazolium chloride (Compound 13, 0.11 g) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionto the residue was added diisopropyl ether (8 ml)
  3. filtrationThe resulting powder was collected by filtration
  4. customflush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=9/1→4/1)
  5. additiona 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 (10 ml)

Sources & evidence

ORD record
ord-b569c515837c49c28206583b759cc34d
Source dataset
uspto-grants-2003_06
Patent number
US06583164B1

Reaction notes

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