1-Methylpiperazine → 1-{[4-(2-Methoxy-5-nitrophenyl)furan-2-yl]methyl}-4-methylpiperazine

HRID 1593789Notes

Reaction equation

HRID 1593789 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[C:12]1[CH:13]=[C:14]([CH:17]=O)[O:15][CH:16]=1.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN1CCCC1=O.C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[C:12]1[CH:13]=[C:14]([CH2:17][N:23]2[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]2)[O:15][CH:16]=1

Participants

7

Reactant 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 160991814-(2-Methoxy-5-nitrophenyl)furan-2-carbaldehyde

Product 1

HCID 160991751-{[4-(2-Methoxy-5-nitrophenyl)furan-2-yl]methyl}-4-methylpiperazineYield 18.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-(2-methoxy-5-nitrophenyl)-2-furaldehyde (230 mg, 0.93 mmol) and N-methylpiperazine (0.90 mL, 8.1 mmol) in 20 mL of dichloromethane and 2 mL of 1-methylpyrolidinone was cooled to 0° C. Sodium triacetoxyborohydride (1.21 g, 5.7 mmol) was added in portions followed by a few drops of acetic acid. The resulting mixture was stirred at 0° C. for 10 minutes then at room temperature for 1.5 hours. The mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography eluting with a gradient of 20% methanol in ethyl acetate to 1% ammonium hydroxide in 20% methanol in ethyl acetate. Trituration with diethyl ether and hexane provided 57 mg (18%) of 1-{[4-(2-methoxy-5-nitrophenyl)-2-furyl]methyl}-4-methylpiperazine as a light yellow solid, 1H NMR (DMSO-d6) δ 2.14 (s, 3H), 2.25-2.36 (broad s, 4H), 2.38-2.46 (broad s, 4H), 3.52 (s, 2H), 4.04 (s, 3H), 6.96 (s, 1H), 7.31 (d, J=8 Hz, 1H), 8.14-8.20 (m, 2H), 8.38 (d, J=3 Hz, 1H); MS 332.1 (M+H)+.

Workup

  1. waitat room temperature for 1.5 hours
  2. customThe mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography
  7. washeluting with a gradient of 20% methanol in ethyl acetate to 1% ammonium hydroxide in 20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-b079a27d5c85452e904acf7a00b043ef
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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