Potassium Carbonate → 4-[4-(3,4-Dihydro-1-methylpyrrolo[1,2-a]pyrazin-6-yl)phenoxy]butan-2-ol fumarate

HRID 486581Notes

Reaction equation

HRID 486581 reaction equation
[OH:1][CH:2]([CH3:16])[CH2:3][CH2:4]OS(C1C(C)=CC=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[OH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[N:34]3[CH2:35][CH2:36][N:37]=[C:38]([CH3:39])[C:33]3=[CH:32][CH:31]=2)=[CH:26][CH:25]=1.[OH-].[Na+].[C:42]([OH:49])(=[O:48])/[CH:43]=[CH:44]/[C:45]([OH:47])=[O:46]>CC(=O)CC.C(O)C>[C:42]([OH:49])(=[O:48])/[CH:43]=[CH:44]/[C:45]([OH:47])=[O:46].[CH3:39][C:38]1[C:33]2[N:34]([C:30]([C:27]3[CH:26]=[CH:25][C:24]([O:23][CH2:4][CH2:3][CH:2]([OH:1])[CH3:16])=[CH:29][CH:28]=3)=[CH:31][CH:32]=2)[CH2:35][CH2:36][N:37]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 444972Fumaric AcidHCID 86747633Toluenesulphonic acid 3-hydroxybutan-1-yl esterHCID 1357369333,4-Dihydro-6-(4-hydroxyphenyl)-1-methylpyrrolo[1,2-a]pyrazine

Product 1

HCID 190953894-[4-(3,4-Dihydro-1-methylpyrrolo[1,2-a]pyrazin-6-yl)phenoxy]butan-2-ol fumarateYield 90%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6569Methyl Ethyl KetoneSolvent

Procedure

Toluenesulphonic acid 3-hydroxybutan-1-yl ester (1.8 g) and 1.8 g of potassium carbonate was added at room temperature while stirring and under argon to a solution of 1.5 g of 3,4-dihydro-6-(4-hydroxyphenyl)-1-methylpyrrolo[1,2-a]pyrazine in 20 ml of 2-butanone and the mixture was boiled for 20 hours. The cooled reaction mixture was treated with 100 ml of 2N sodium hydroxide solution and extracted three times with 200 ml of methylene chloride each time. The organic phases were washed twice with 100 ml of water each time, combined, dried with MgSO4 and freed from solvent. The residue, 2.4 g of brown oil, was chromatographed on 50 g of silica gel with methylene chloride/methanol mixtures (50:1 to 20:1) as the eluent. There were obtained 1.2 g of an orange coloured, amorphous solid which was dissolved in a 25-fold amount of ethanol and treated while hot with 1.1 equivalents of a saturated solution of fumaric acid in ethanol. There were obtained 1.5 g (90%) of 4-[4-(3,4-dihydro-1-methylpyrrolo[1,2-a]pyrazin-6-yl)phenoxy]butan-2-ol fumarate (1:1); m.pt.: 156°-157° C. (dec.).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted three times with 200 ml of methylene chloride each time
  3. washThe organic phases were washed twice with 100 ml of water each time
  4. dry with materialdried with MgSO4
  5. customThe residue, 2.4 g of brown oil, was chromatographed on 50 g of silica gel with methylene chloride/methanol
  6. customThere were obtained 1.2 g of an orange coloured, amorphous solid which

Sources & evidence

ORD record
ord-352821f482ef425f8db03bdfcb9ee2e1
Source dataset
uspto-grants-1994_03
Patent number
US05292732

Reaction notes

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