Ethanol → Olanzapine

HRID 251392Notes

Reaction equation

HRID 251392 reaction equation
[NH2:1][C:2]1[C:3]2[CH:15]=[C:14]([CH3:16])[S:13][C:4]=2[NH:5][C:6]2[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=2[N:8]=1.[CH3:17][N:18]1[CH2:23][CH2:22]N[CH2:20][CH2:19]1.C(O)C>O>[CH3:16][C:14]1[S:13][C:4]2[NH:5][C:6]3[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=3[N:8]=[C:2]([N:1]3[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19][CH2:20]3)[C:3]=2[CH:15]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 531671-MethylpiperazineHCID 135446208Olanzamine

Product 1

HCID 135398745OlanzapineYield 72%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
94 °C

Procedure

4-Amino-2-methyl-10H-thieno-[2,3-b][1,5]benzodiazepine (5 g, 0.02 mol), N-methylpiperazine (12.5 mL, 2.5 vol) and ethanol (15 mL, 3 vol) were charged into a three-necked round bottom flask equipped with a reflux condenser, overhead stirrer, and thermometer. The reaction mixture was slowly heated to reflux (94° C.) under a nitrogen atmosphere and kept at this temperature overnight. The reaction mixture was cooled to below 50° C. and water (10 mL, 2 vol) was added to precipitate out the solid, which was isolated by filtration. The light yellow solid was washed twice with water (5 mL) and dried to furnish pure olanzapine in 72% yield (4.2 g).

Workup

  1. customequipped with a reflux condenser, overhead stirrer
  2. temperatureThe reaction mixture was slowly heated
  3. customkept at this temperature overnight
  4. temperatureThe reaction mixture was cooled to below 50° C.
  5. customto precipitate out the solid
  6. customwhich was isolated by filtration
  7. washThe light yellow solid was washed twice with water (5 mL)
  8. customdried

Sources & evidence

ORD record
ord-fd398bc5762e428693a590d43f91e5df
Source dataset
uspto-grants-2011_01
Patent number
US07863442B2

Reaction notes

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