4-Fluorobenzyl chloride → HCID 9797495, compound

HRID 1018937Notes

Reaction equation

HRID 1018937 reaction equation
O1C2C=CC(N3CCNCC3)=CC=2OCC1.C(O)(=O)C(O)=O.[O:23]1[C:28]2[CH:29]=[CH:30][C:31]([N:33]3[CH2:38][CH2:37][N:36]([CH2:39][C:40]4[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=4)[CH2:35][CH2:34]3)=[CH:32][C:27]=2[O:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[K+].[K+].FC1C=CC(CCl)=CC=1>CC#N>[O:23]1[C:28]2[CH:29]=[CH:30][C:31]([N:33]3[CH2:34][CH2:35][N:36]([CH2:39][C:40]4[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=4)[CH2:37][CH2:38]3)=[CH:32][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 96024-Fluorobenzyl chlorideHCID 11430Potassium CarbonateHCID 10713381-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-piperazineHCID 18399633HCID 18399633, compound

Product 1

HCID 9797495HCID 9797495, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-(1,4-benzodioxan-6-yl)piperazine prepared as described in Example 1 (0.146 g, 0.663 mmol) in CH3CN (5 mL) is treated with potassium carbonate (0.458 g, 3.32 mmol) and 4-fluorobenzyl chloride (0.144 g, 0.995 mmol). The mixture is heated at reflux for 4 hours. The resulting mixture is then cooled to room temperature and washed successively with saturated aqueous NH4Cl (20 mL) and saturated aqueous NaCl (20 mL). The organic portion is dried over Mg2SO4, filtered and concentrated. Purification by flash column chromatography (30% ethyl acetate-hexane) gives 0.074 g (34%) of 1-(1,4 benzodioxan-6-yl)-4-(4-fluorobenzyl)piperazine as a white solid (TLC Rf 0.35; 30% ethyl acetate:hexane). A solution of this material in 1 mL of ethanol is treated with oxalic acid (0.020 g, 0.225 mmol) and concentrated to give 1-(1-(1,4-benzodioxan-6-yl)-4-(4-fluorobenzyl)piperazine oxalic acid salt (Compound 1) 0.079 g (88%), m.p. 177-179° C.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 4 hours
  3. washwashed successively with saturated aqueous NH4Cl (20 mL) and saturated aqueous NaCl (20 mL)
  4. dry with materialThe organic portion is dried over Mg2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash column chromatography (30% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a7a6ab4e7b734864b4d8bca1c1c3b30b
Source dataset
uspto-grants-2002_11
Patent number
US06486164B2

Reaction notes

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