Acetic Acid → HCID 11794984, compound

HRID 1729150Notes

Reaction equation

HRID 1729150 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[CH3:3].[Br:17][C:18]1[CH:19]=[C:20]([CH:23]=O)[S:21][CH:22]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C.ClC(Cl)C>>[Br:17][C:18]1[CH:19]=[C:20]([CH2:23][N:14]2[CH2:13][CH2:12][N:11]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[O:4][CH:2]([CH3:1])[CH3:3])[CH2:16][CH2:15]2)[S:21][CH:22]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 877924-Bromothiophene-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 109440161-[2-(Propan-2-yloxy)phenyl]piperazine

Product 1

HCID 11794984HCID 11794984, compoundYield 98.8%

Procedure

A mixture of 1-[2-(methylethoxy)phenyl]piperazine (6.30 g, 0.029 mol), prepared as described by Martin and Scott, et al., J. Med. Chem., 1989, 32, 1052-1056, 4-bromo-2-thiophenecarboxaldehyde (5.50 g, 0.029 mol), NaBH(OAc)3 (8.00 g, 0.038 mol), acetic acid (1.70 g, 0.029 mol), and dichloroethane was stirred for several hours at room temperature. The reaction was then partitioned between diethyl ether/aqueous 10% Na2CO3 and the ether layer was separated, washed with saturated NaCl solution, dried over anhydrous K2CO3, filtered, and evaporated to give 1-[(4-bromo-2-thienyl) methyl]-4-[2-(1-methylethoxy)phenyl]piperazine (11.33 g) as a crude oil. Treatment of this material with HCl diethyl ether-isopropanol gave a crystalline solid which was recrystallized from methanol to give 1-[(4-bromo-2-thienyl)methyl]-4-[2-(1-methylethoxy) phenyl]piperazine monohydrochloride (10 g, 77%). A 2.0 g sample of this was recrystallized twice from methanol, and chromatographed on flash silica (99:1/CHCl3 :MeOH with 1% NH4OH as eluant). The resulting oil was converted to the hydrochloride salt, as described previously, and was recrystallized from methanol , and dried to give 1-[(4-bromo-2-thienyl) methyl]-4-[2-(1-methylethoxy) phenyl]piperazine monohydrochloride, m.p. (darkens 240° C.) 243°-249.5° C. 1H NMR and CI MS support the structure.

Workup

  1. customprepared
  2. customThe reaction was then partitioned between diethyl ether/aqueous 10% Na2CO3
  3. customthe ether layer was separated
  4. washwashed with saturated NaCl solution
  5. dry with materialdried over anhydrous K2CO3
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-e30feba721a9412b9c08771ac3d54743
Source dataset
uspto-grants-1994_07
Patent number
US05332732

Reaction notes

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