Methanol → Olanzapine

HRID 251393Notes

Reaction equation

HRID 251393 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.CO>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 887MethanolHCID 531671-MethylpiperazineHCID 135446208Olanzamine

Product 1

HCID 135398745OlanzapineYield 74%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
75 °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 methanol (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 under nitrogen to reflux (75° C.) and kept at this temperature overnight. The reaction mixture was allowed to cool to below 50° C. and water (15 mL, 3 vol) was added. The precipitated light yellow solid was isolated by filtration, then was washed twice with water (5 mL) and dried to provide olanzapine in 74% yield (4.35 g).

Workup

  1. customequipped with a reflux condenser, overhead stirrer
  2. temperatureThe reaction mixture was slowly heated under nitrogen
  3. customkept at this temperature overnight
  4. temperatureto cool to below 50° C.
  5. customThe precipitated light yellow solid was isolated by filtration
  6. washwas washed twice with water (5 mL)
  7. customdried

Sources & evidence

ORD record
ord-35ae15d6dece4bcba9a8deea112247c8
Source dataset
uspto-grants-2011_01
Patent number
US07863442B2

Reaction notes

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