Norchlorcyclizine → 4-[4-(4-Chlorobenzhydryl)piperazino]methyl-2-dimethylaminophenol

HRID 1032954Notes

Reaction equation

HRID 1032954 reaction equation
[CH3:1][N:2]([CH3:12])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[OH:11])[CH:6]=O.CN(C)C1C=C(C=CC=1OCOC)C=O.[Cl:28][C:29]1[CH:47]=[CH:46][C:32]([CH:33]([N:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[CH:31][CH:30]=1.[Na].C(=O)([O-])O.[Na+]>CO.O.C(O)(=O)C>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([CH:33]([N:40]2[CH2:41][CH2:42][N:43]([CH2:6][C:5]3[CH:8]=[CH:9][C:10]([OH:11])=[C:3]([N:2]([CH3:12])[CH3:1])[CH:4]=3)[CH2:44][CH2:45]2)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[CH:46][CH:47]=1

Participants

9

Reactant 5

HCID 9340NorchlorcyclizineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 19026975HCID 19026975, compoundHCID 19026982HCID 19026982, compound

Product 1

HCID 190269934-[4-(4-Chlorobenzhydryl)piperazino]methyl-2-dimethylaminophenol

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 3-dimethylamino-4-hydroxybenzaldehyde (see Synthesis of Compound A) (600 mg, 3.63 mmol) in methanol (10 ml) was added 1-(4-chlorobenzhydryl)piperazine (1.25 g, 4.36 mmol) while stirring at room temperature. Thereto was added sodium cianoborohydride (95% content) (700 mg, 10.6 mmol) by portions. After stirring for 1 hour, acetic acid (0.2 ml) was added thereto, and the mixture was further stirred for 3 hours. The reaction mixture was poured into water, and the pH of the solution was made basic by the addition of a saturated aqueous solution of sodium hydrogencarbonate. The solution was extracted with ethyl acetate and washed with a saturated aqueous solution of sodium hydrogencarbonate. The extract was then extracted with 1N hydrochloric acid, and the aqueous layer was neutralized and extracted with ethyl acetate. Then thus obtained extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel to give the object Compound 7. Yield 569 mg (36%).

Workup

  1. stirringAfter stirring for 1 hour
  2. stirringthe mixture was further stirred for 3 hours
  3. extractionThe solution was extracted with ethyl acetate
  4. washwashed with a saturated aqueous solution of sodium hydrogencarbonate
  5. extractionThe extract was then extracted with 1N hydrochloric acid
  6. extractionextracted with ethyl acetate
  7. customThen thus obtained
  8. extractionextract
  9. washwas washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customevaporated
  12. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-9955c8da5e2b493c8651a8c9156da51b
Source dataset
uspto-grants-1994_05
Patent number
US05308840

Reaction notes

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