1-Methylpiperazine → Olanzapine

HRID 251388Notes

Reaction equation

HRID 251388 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>CC(O)C>[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

4

Reactant 2

HCID 531671-MethylpiperazineHCID 135446208Olanzamine

Product 1

HCID 135398745OlanzapineYield 80%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

4-Amino-2-methyl-10H-thieno-[2,3-b][1,5]benzodiazepine (50 g, 0.19 mol), N-methylpiperazine (125 mL, 2.5 vol) and 2-propanol (150 mL, 3 vol) were charged into a three-necked round bottom flask, equipped with reflux condenser, overhead stirrer, and thermometer. The reaction mixture was heated to reflux (about 100° C.) slowly under a nitrogen atmosphere and then refluxed overnight. The reaction mixture was allowed to cool slowly to below 40° C. (about 1 h), whereupon solid precipitates out. This precipitate was then isolated by filtration and the resulting light yellow solid was twice washed with 2-propanol (100 mL). The light yellow solid was stirred with water (4 volumes) for 2.5 hours, filtered, and the resulting solid, was washed twice with water (2 volumes) and dried to furnish olanzapine (47 g, 80%).

Workup

  1. customequipped
  2. temperaturewith reflux condenser
  3. temperatureThe reaction mixture was heated
  4. temperaturerefluxed overnight
  5. temperatureto cool slowly to below 40° C. (about 1 h)
  6. customwhereupon solid precipitates out
  7. customThis precipitate was then isolated by filtration
  8. washthe resulting light yellow solid was twice washed with 2-propanol (100 mL)
  9. filtrationfiltered
  10. washthe resulting solid, was washed twice with water (2 volumes)
  11. customdried

Sources & evidence

ORD record
ord-c29e6813acf240d7b0ca34e0b809b0c5
Source dataset
uspto-grants-2011_01
Patent number
US07863442B2

Reaction notes

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