Chloromethyl Methyl Ether → 1-[4-(Methoxymethoxy)phenyl]-4-(4-nitrophenyl)piperazine

HRID 527174Notes

Reaction equation

HRID 527174 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(NC(C)C)(C)C.[CH3:30][O:31][CH2:32]Cl>C(Cl)Cl>[CH3:30][O:31][CH2:32][O:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 7912DiisopropylamineHCID 113810174-[4-(4-Nitrophenyl)piperazin-1-yl]phenol

Product 1

HCID 565937061-[4-(Methoxymethoxy)phenyl]-4-(4-nitrophenyl)piperazineYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 10 (263.4 mg, 0.88 mmol) and diisopropylamine (DIPEA) (170.6 mg, 1.32 mmol) in CH2Cl2 (12 mL) was added slowly chloromethyl methyl ether (77.9 mg, 0.97 mmol) at room temperature. The reaction was stirred for 16 h, and then quenched by the addition of saturated aqueous ammonium chloride (10 mL). The resulting solution was extracted with more CH2O2, dried (Na2SO4), filtered, and concentrated to yield the crude product, which was purified by column chromatography (neat CH2Cl2→100:1 CH2Cl2-Acetone) to afford 11 (250.8 mg, 83%) as a yellow amorphous solid; 1H NMR (400 MHz, CDCl3, δH) 8.20-8.08 (m, 2H), 7.07-6.97 (m, 2H), 6.97-6.82 (m, 4H), 5.13 (s, 2H), 3.62-3.51 (m, 4H), 3.48 (s, 3H), 3.30-3.18 (m, 4H); 13C NMR (100 MHz, CDCl3, δC) 154.99, 151.98, 146.31, 138.84, 126.18, 118.59, 117.58, 113.04, 95.28, 56.13, 50.42, 47.43. MALDI-MS: 344.2 (M+H+), 366.2 (M+Na+).

Workup

  1. customquenched by the addition of saturated aqueous ammonium chloride (10 mL)
  2. extractionThe resulting solution was extracted with more CH2O2
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield the crude product, which
  7. customwas purified by column chromatography (neat CH2Cl2→100:1 CH2Cl2-Acetone)

Sources & evidence

ORD record
ord-1b9d8a2e50ed46faba9cea44c3fba3a2
Source dataset
uspto-grants-2016_05
Patent number
US09346791B2

Reaction notes

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