Acetic Acid → Quilostigmine

HRID 2209744Notes

Reaction equation

HRID 2209744 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=[CH:9]1)([N:3]1[CH:7]=[CH:6]N=[CH:4]1)=O.[C:13]([OH:16])(=[O:15])C.[CH2:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][NH:18]1>C(OCC)(=O)C>[CH2:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][N:18]1[C:13]([O:16][C:20]1[CH:21]=[C:22]2[C:12](=[CH:11][CH:19]=1)[N:8]([CH3:9])[C@H:1]1[N:3]([CH3:4])[CH2:7][CH2:6][C@@:23]21[CH3:24])=[O:15]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 70461,2,3,4-TetrahydroisoquinolineHCID 682631,1'-Carbonyldiimidazole

Product 1

HCID 132228QuilostigmineYield 161%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To the ethyl acetate solution (which contained (-)-eseroline) was added, under N2, 13.17 g (1.0 equiv) of 1,1'-carbonyldiimidazole, as a solid, in several portions. This was followed by the addition of 13.16 g (3.0 equiv) of glacial acetic acid and 10.81 g (1.07 equiv) of 1,2,3,4-tetrahydroisoquinoline in 20 mL of ethyl acetate. After stirring overnight, the reaction mixture was extracted with 200 mL of water. The ethyl acetate solution was further extracted twice with 100 mL of 0.5N sodium hydroxide solution, and 100 mL of water. After drying over anhydrous sodium sulfate, the ethyl acetate solution was concentrated under reduced pressure to give 24.66 g (80.5%) of crude product.

Workup

  1. extractionthe reaction mixture was extracted with 200 mL of water
  2. extractionThe ethyl acetate solution was further extracted twice with 100 mL of 0.5N sodium hydroxide solution, and 100 mL of water
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. concentrationthe ethyl acetate solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b70d0fd034b44a80ae426033f85a2fb1
Source dataset
uspto-grants-1995_10
Patent number
US05455354

Reaction notes

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