Bis(2-bromoethyl) ether → 4-(4-bromo-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine

HRID 1622441Notes

Reaction equation

HRID 1622441 reaction equation
[Br:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:11])[NH:10][C:6]=2[CH:5]=[C:4]([NH2:12])[CH:3]=1.Br[CH2:14][CH2:15][O:16][CH2:17][CH2:18]Br.CCN(C(C)C)C(C)C>C(O)CO.O>[Br:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:11])[NH:10][C:6]=2[CH:5]=[C:4]([N:12]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:3]=1

Participants

6

Reactant 3

HCID 21521Bis(2-bromoethyl) etherHCID 81531DiisopropylethylamineHCID 837094637-bromo-2-methyl-3H-benzo[d]imidazol-5-amine

Product 1

HCID 569605414-(4-bromo-2-methyl-1H-benzo[d]imidazol-6-yl)morpholineYield 58%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-bromo-2-methyl-3H-benzo[d]imidazol-5-amine (25 g, 111 mmol), 1-bromo-2-(2-bromoethoxy)ethane (38 g, 166 mmol) and DIPEA (21 g, 166 mmol) in ethylene glycol (600 mL) was stirred at 100° C. for 20 h. It was cooled to rt, and diluted with water (200 mL) and extracted with DCM (300 mL×4). The combined organic layers were washed with brine, dried over sodium sulphate and evaporated. The residue was purified by column chromatography (eluted with petroleum ether/ethyl acetate=1/1) to give the product (19 g, 58%) as a yellow solid; LC/MS: MS (ES+) m/e 296 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 2.44 (s, 3H), 3.07 (t, J=4.8 Hz, 4H), 3.74 (t, J=4.8 Hz, 4H), 6.85 (d, J=2.1 Hz, 1H), 7.04 (d, J=2.1 Hz, 1H), 12.20 (s, 1H).

Workup

  1. temperatureIt was cooled to rt
  2. extractionextracted with DCM (300 mL×4)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. customevaporated
  6. customThe residue was purified by column chromatography (eluted with petroleum ether/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-66651d25e2ef41169313e3140b94d2d6
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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