(+-)-2-Butanol → Olanzapine

HRID 251389Notes

Reaction equation

HRID 251389 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)CC>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 6568(+-)-2-ButanolHCID 531671-MethylpiperazineHCID 135446208Olanzamine

Product 1

HCID 135398745OlanzapineYield 84%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
118 °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-butanol (200 mL, 2 vol) were charged into a three-necked round bottom flask equipped with a reflux condenser, overhead stirrer, and thermometer. The reaction mixture was heated to reflux at 118° C. under a nitrogen atmosphere and refluxed overnight. The reaction mixture was allowed to cool to below 55° C. whereupon water (300 mL, 3 volumes) was added to precipitate out the solid. It was isolated by Buchner filtration and the light yellow solid was washed twice with 25% aqueous 2-butanol (100 mL) and then once with 2-butanol (100 mL) and dried to provide olanzapine in 84% yield (98.7 g).

Workup

  1. customequipped with a reflux condenser, overhead stirrer
  2. temperatureThe reaction mixture was heated
  3. temperaturerefluxed overnight
  4. additionwas added
  5. customto precipitate out the solid
  6. customIt was isolated by Buchner filtration
  7. washthe light yellow solid was washed twice with 25% aqueous 2-butanol (100 mL)
  8. dry with materialonce with 2-butanol (100 mL) and dried

Sources & evidence

ORD record
ord-8de9679efb234850a41c1c5a71966a25
Source dataset
uspto-grants-2011_01
Patent number
US07863442B2

Reaction notes

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