Propanal → 1-[2,4-bis (4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepin-3-yl]-1-propanol

HRID 1782396Notes

Reaction equation

HRID 1782396 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH2:9][C:10]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[N:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:4][CH2:3]1.C([N-]C(C)C)(C)C.[Li+].[CH:34](=[O:37])[CH2:35][CH3:36].O>O1CCCC1.C(Cl)(Cl)Cl>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([C:8]2[CH:9]([CH:34]([OH:37])[CH2:35][CH3:36])[C:10]([N:19]3[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)=[N:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 527PropanalHCID 962WaterHCID 2724682Lithium diisopropylamideHCID 117248372,4-Bis(4-methyl-1-piperazinyl)-3H-1,5-benzodiazepine

Product 1

HCID 100238171-[2,4-bis (4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepin-3-yl]-1-propanolYield 92%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

A suspension of 2,4-bis(4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepine (17.024 g, 50 mmol) in tetrahydrofuran (200 ml) under constant flow of argon was cooled to −30° C. A solution of lithium diisopropylamide (LDA) (2 M, 37.5 ml, 75 mmol) was added dropwise. Thus obtained dark brown suspension was allowed to warm to −5° C., and then again cooled to −30° C. Propionaldehyde (5.50 ml, 75 mmol) was added during 5 min. The resulting pale brown suspension was allowed to warm to 10° C., while strongly agitated water (250 ml) was added. The solution was transferred to a separating funnel, chloroform (150 ml) was added and the phases were separated. The water phase was extracted with chloroform (2×50 ml). The combined organic phases were dried over anhydrous Na2SO4 and the solvent was evaporated at reduced pressure. The crude product was suspended in hexane (750 ml), filtered off and washed with hexane (75 ml) to give 18.34 g (92%) of the title compound as an off-white powder. For analytical purposes the product was recrystallised from ethyl acetate.

Workup

  1. temperatureto warm to −5° C.
  2. temperatureagain cooled to −30° C
  3. additionwas added
  4. customThe solution was transferred to a separating funnel
  5. customthe phases were separated
  6. extractionThe water phase was extracted with chloroform (2×50 ml)
  7. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  8. customthe solvent was evaporated at reduced pressure
  9. filtrationfiltered off
  10. washwashed with hexane (75 ml)

Sources & evidence

ORD record
ord-e7a00b85ee584f81a8e05b4ea71e8100
Source dataset
uspto-grants-2009_03
Patent number
US07498433B2

Reaction notes

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