Ethyl chloroformate → HCID 70173142, compound

HRID 1069364Notes

Reaction equation

HRID 1069364 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]4[C:23](=[O:24])[C:22]5=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]5[C:20]4=[O:29])[CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.Cl[C:31]([O:33][CH2:34][CH3:35])=[O:32].[C:36]([O-:39])([OH:38])=O.[Na+]>O>[C:23]([OH:32])(=[O:24])/[CH:22]=[CH:25]\[C:36]([OH:39])=[O:38].[CH2:34]([O:33][C:31]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=2)[C:6]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]3[C:23](=[O:24])[C:22]4=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]4[C:20]3=[O:29])[CH2:13][CH2:12]2)=[N:7]1)=[O:32])[CH3:35]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformate2×HCID 516892Sodium BicarbonateHCID 18467209N-[2-[4-(6-fluoro1H-indazol-3-yl)-1-piperazinyl]ethyl]phthalimide

Product 1

HCID 70173142HCID 70173142, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of N-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinyl]ethyl]phthalimide (1.8 g, 4.6 mmol) and ethyl chloroformate (5.7 g, 52.3 mmol) was heated on a stream bath for 10 minutes. The reaction was cooled and an additional 2.3 g (20.9 mmol) ethyl chloroformate was added. The reaction was returned to the steam bath for 10 minutes longer and then cooled. The resultant solid was triturated with anhydrous Et2O and collected to yield 2.0 g. The solid was suspended in H2O (100 ml) and NaHCO3 was added to make the pH=8. The aqueous mixture was extracted with CH2Cl2 and the CH2Cl2 extract was washed with H2O, dried with Na2SO4 and concentrated to afford 2.0 g of a yellow oil that crystallized readily. The product was flashed over 80 g silica gel using 2% Et2NH-EtOAc as eluent to afford 1.10 g (2.36 mmol) of an off-white solid. The compound was dissolved in hot absolute ethanol (55 ml) and maleic add (0.28 g, 2.36 mmol) was added. The solution was refluxed gently for 10 minutes and then cooled. Most of the ethanol was removed in vacuo and the resultant white suspension was diluted with anhydrous Et2O (50 ml). The solid that was produced was collected to yield 1.35 g. Recrystallization from CH3CN gave 1.15 g of the maleate salt as a white powder, m.p. 214-216° C.

Workup

  1. temperaturewas heated on a stream bath for 10 minutes
  2. temperatureThe reaction was cooled
  3. temperaturelonger and then cooled
  4. customThe resultant solid was triturated with anhydrous Et2O
  5. customcollected
  6. customto yield 2.0 g
  7. extractionThe aqueous mixture was extracted with CH2Cl2
  8. extractionthe CH2Cl2 extract
  9. washwas washed with H2O
  10. dry with materialdried with Na2SO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-88f1994f5d5b4f7690a53ae37fea1741
Source dataset
uspto-grants-2001_06
Patent number
US06251907B1

Reaction notes

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