Diisopropyl Ether → HCID 58763939, compound

HRID 859197Notes

Reaction equation

HRID 859197 reaction equation
[C:1]([O:4][C:5]1[C:6]([C:24]([OH:26])=O)=[N:7][N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])[C:9]=1[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)(=[O:3])[CH3:2].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[F:45][C:46]([F:53])([CH3:52])[CH2:47][NH:48][CH2:49][CH2:50][OH:51].C(OC(C)C)(C)C>C(Cl)Cl>[Cl:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[N:8]1[C:9]([C:10]2[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=2)=[C:5]([O:4][C:1](=[O:3])[CH3:2])[C:6]([C:24](=[O:26])[N:48]([CH2:47][C:46]([F:53])([F:45])[CH3:52])[CH2:49][CH2:50][OH:51])=[N:7]1

Participants

7

Reactant 5

HCID 7914Diisopropyl EtherHCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 27583572-(2,2-difluoropropylamino)ethanolHCID 58763934HCID 58763934, compound

Product 1

HCID 58763939HCID 58763939, compoundYield 79.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Acetoxy-1-(2-chlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid I-6d (581.0 g, 1.48 mol) was dissolved in 10 liters of methylene chloride to give a pale yellow, slightly opaque solution. The solution was filtered through Celite® to give a clear green colored solution. 2-Chloro-4,6-dimethoxy-1,3,5-triazine (296.8 g, 1.64 mol) was added in one portion as a solid at room temperature to give an opaque suspension (addition is slightly endothermic). 4-Methylmorpholine (182.9 g, 1.80 mol) was added over 15 minutes while keeping the temperature between 18–22° C. (reaction returned to being yellow in color). Reaction stirred for 3 hours at room temperature, then 2-(2,2-difluoropropylamino)-ethanol (228.3 g, 1.64 mol) was added neat over 10 minutes while keeping the temperature between 20–25° C. The reaction was stirred for 15 hours, then washed twice with 6 liter portions of 10% citric acid and once with 5 liters of brine. The crude product solution was concentrated in vacuo to a thick orange oil, then reconstituted in 4 liters of isopropyl ether. After removing 1 liter of distillates precipitate began to form. To the crude product suspension was added 1.5 liters of isopropyl ether and then the mixture was stirred at room temperature for 1 hour. The precipitated solids were collected by filtration and the resulting filtercake was rinsed with 2 liters of room temperature isopropyl ether, followed by air-drying for 16 hours. Acetic acid 1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-[(2,2-difluoro-propyl)-(2-hydroxyethyl)-carbamoyl]-1H-pyrazol-4-yl ester I-6e (603.0 g, 78%) was isolated as a granular off-white solid.

Workup

  1. customto give a pale yellow, slightly opaque solution
  2. filtrationThe solution was filtered through Celite®
  3. customto give a clear green colored solution
  4. customto give an opaque suspension (
  5. additionaddition
  6. custombetween 18–22° C.
  7. custom(reaction returned to being yellow in color)
  8. customReaction
  9. custombetween 20–25° C
  10. stirringThe reaction was stirred for 15 hours
  11. washwashed twice with 6 liter portions of 10% citric acid and once with 5 liters of brine
  12. concentrationThe crude product solution was concentrated in vacuo to a thick orange oil
  13. customAfter removing 1 liter of distillates precipitate
  14. customto form
  15. stirringthe mixture was stirred at room temperature for 1 hour
  16. filtrationThe precipitated solids were collected by filtration
  17. washthe resulting filtercake was rinsed with 2 liters of room temperature isopropyl ether
  18. customby air-drying for 16 hours

Sources & evidence

ORD record
ord-93be755a608a4eb192cc9c77277f4d5c
Source dataset
uspto-grants-2006_12
Patent number
US07151097B2

Reaction notes

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