Isopropanol → Olanzapine

HRID 251390Notes

Reaction equation

HRID 251390 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>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 3776IsopropanolHCID 531671-MethylpiperazineHCID 135446208Olanzamine

Product 1

HCID 135398745OlanzapineYield 86.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
102 °C

Procedure

4-Amino-2-methyl-10H-thieno-[2,3-b][1,5]benzodiazepine (100 g, 0.38 mol), N-methylpiperazine (250 mL, 2.5 vol) and 2-propanol (200 mL, 2 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 at 102° C. under a nitrogen atmosphere overnight. The reaction mixture was allowed to cool to below 55° C. whereupon water (250 mL, 2.5 volumes) was added to precipitate out the solid. The light yellow solid was isolated by Buchner filtration and twice washed with 25% aqueous 2-propanol (100 mL) and then once with 2-propanol (100 mL). It was dried in vacuo to provide olanzapine in 86.5% yield (101.7 g).

Workup

  1. customequipped
  2. temperaturewith reflux condenser
  3. temperatureThe reaction mixture was heated
  4. additionwas added
  5. customto precipitate out the solid
  6. customThe light yellow solid was isolated by Buchner filtration
  7. washtwice washed with 25% aqueous 2-propanol (100 mL)
  8. customIt was dried in vacuo

Sources & evidence

ORD record
ord-7d84afc7ef274298b5826691e9176ff0
Source dataset
uspto-grants-2011_01
Patent number
US07863442B2

Reaction notes

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