1-(2-Methoxyphenyl)piperazine → 4-(2-Methoxyphenyl)piperazine-1-carbaldehyde

HRID 1876819Notes

Reaction equation

HRID 1876819 reaction equation
[CH3:1][N:2]([CH:4]=[O:5])[CH3:3].C(OC1C(OC)=CC(C(O)=O)=C([N+]([O-])=O)C=1)(=O)C1C=CC=CC=1.S(Cl)(Cl)=O.[CH3:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N:41]1[CH2:46]CNC[CH2:42]1>C1C=CC=CC=1.C(N(CC)CC)C>[CH3:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N:41]1[CH2:42][CH2:3][N:2]([CH:4]=[O:5])[CH2:1][CH2:46]1

Participants

7

Reactant 4

HCID 13461-(2-Methoxyphenyl)piperazineHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 594400844-Benzoyloxy-5-methoxy-2-nitro benzoic acid

Product 1

HCID 73261424-(2-Methoxyphenyl)piperazine-1-carbaldehydeYield 93%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8471TriethylamineSolvent

Procedure

DMF was added to a stirred suspension of 4-benzoyloxy-5-methoxy-2-nitro benzoic acid (6) (0.500 mg, 1.65 mmol) and thionyl chloride (3 ml) in dry benzene (30 ml) and the stirring was continued for 6 h. The benzene was evaporated in vacuum and the resultant oil dissolved in dry THF (50 ml) and added drop wise over a period of 1 h to a stirred suspension of 1-(2-methoxyphenyl)piperazine (316 mg 15.6 mmol) triethyl amine (5 ml). After the completion of addition, the reaction mixture was brought to ambient temperature and stirred for an additional hour. The THF was evaporated in vacuum and the aqueous layer was washed with ethyl acetate. The aqueous phase was then adjusted to pH 3 using 6 N HCl and extracted with ethyl acetate and washed with brine, dried over Na2SO4 and evaporated in vacuum to afford the crude product of 2-amino-4-benzyloxy)-5-methoxyphenyl][4-(2-methoxyphenyl)piperazino]methanone (7a) in 93% yield (670 mg, 85% yield). 1H NMR (CDCl3) δ 3.20-3.30 (m, 4H), 3.40-3.55 (m, 4H), 3.85 (S, 3H), 3.95 (s, 3H), 5.20 (s, 2H), 6.80-7.00 (m, 5H), 7.30-7.50 (m, 5H), 7.70 (s, 1H); FABMS: 477 (M+H)+.

Workup

  1. customThe benzene was evaporated in vacuum
  2. dissolutionthe resultant oil dissolved in dry THF (50 ml)
  3. additionadded drop wise over a period of 1 h
  4. additionAfter the completion of addition
  5. customwas brought to ambient temperature
  6. customThe THF was evaporated in vacuum
  7. washthe aqueous layer was washed with ethyl acetate
  8. extractionextracted with ethyl acetate
  9. washwashed with brine
  10. dry with materialdried over Na2SO4
  11. customevaporated in vacuum

Sources & evidence

ORD record
ord-9b9d1db2960248389b5098c4773dd01c
Source dataset
uspto-grants-2012_11
Patent number
US08309726B2

Reaction notes

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