Nefazodone → Nefazodone Hydrochloride

HRID 482787

Reaction equation

HRID 482787 reaction equation
[Na].O(CCBr)C1C=CC=CC=1.[Cl:12][C:13]1[CH:14]=[C:15]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27][N:28]3[C:32](=[O:33])[N:31]([CH2:34][CH2:35][O:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:30]([CH2:43][CH3:44])=[N:29]3)[CH2:21][CH2:20]2)[CH:16]=[CH:17][CH:18]=1>C1(C)C(C)=CC=CC=1>[ClH:12].[Cl:12][C:13]1[CH:14]=[C:15]([N:19]2[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][CH2:27][N:28]3[C:32](=[O:33])[N:31]([CH2:34][CH2:35][O:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:30]([CH2:43][CH3:44])=[N:29]3)[CH2:23][CH2:24]2)[CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 4449NefazodoneHCID 68526Benzene, (2-bromoethoxy)-HCID 5360545Sodium

Product 1

HCID 54911Nefazodone HydrochlorideYield 30.7%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent2×

Procedure

The sodium salt is pulverized, suspended in 200 ml. of xylene and mixed with phenoxyethyl bromide (10.4 g., 0.052 mole) in 20 ml. of xylene. The resulting mixture is refluxed with stirring for a 64 hr. period and the hot reaction mixture filtered. The filtrate is concentrated under reduced pressure and residual material taken up in ether. Insolubles are collected and the ether filtrate concentrated to afford 22.9 g. (94%) of 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl-4-(2-phenoxyethyl)-2H-1,2,4-triazol-3(4H)-one as the free base. Purification of the product is carried out by acidifying a solution of the free base in ethanol with ethanolic hydrogen chloride, and crystallization to afford hydrated (0.25 mole) 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl-4-(2-phenoxyethyl)-2H-1,2,4-triazol-3(4H)-one hydrochloride, m.p. 175°-177° C. (30.7% yield).

Workup

  1. temperatureThe resulting mixture is refluxed
  2. filtrationperiod and the hot reaction mixture filtered
  3. concentrationThe filtrate is concentrated under reduced pressure and residual material
  4. customInsolubles are collected
  5. concentrationthe ether filtrate concentrated
  6. customto afford 22.9 g
  7. customPurification of the product
  8. customwith ethanolic hydrogen chloride, and crystallization

Sources & evidence

ORD record
ord-b87a59b3c9564f8aacedc74b1ae53c34
Source dataset
uspto-grants-1986_03
Patent number
US04575555

Linked notes

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