Hydrochloric Acid → N-{2-[4-(2,3-Dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propyl}pyridin-2-amine

HRID 9738Notes

Reaction equation

HRID 9738 reaction equation
C(OC(=O)[N:7]([CH2:14][CH:15]([N:17]1[CH2:22][CH2:21][N:20]([C:23]2[C:32]3[O:31][CH2:30][CH2:29][O:28][C:27]=3[CH:26]=[CH:25][CH:24]=2)[CH2:19][CH2:18]1)[CH3:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1)(C)(C)C.Cl>C(O)C>[O:28]1[C:27]2[CH:26]=[CH:25][CH:24]=[C:23]([N:20]3[CH2:21][CH2:22][N:17]([CH:15]([CH3:16])[CH2:14][NH:7][C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=4)[CH2:18][CH2:19]3)[C:32]=2[O:31][CH2:30][CH2:29]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 10288411{2-[4-(2,3-Dihydro-benzo[1,4]dioxin-5-yl)-piperazin-1-yl]-propyl}-pyridin-2-yl-carbamic acid tert-butyl ester

Product 1

HCID 12991319N-{2-[4-(2,3-Dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]propyl}pyridin-2-amineYield 49%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Compound VII as a crude oil (49.0 g, 0.106 mol) is dissolved in ethanol (150 mL) and to this solution is added 1N HCl solution in ethanol (212 mL). The resulting solution is refluxed for 18 h, then concentrated in vacuum to a small volume (˜100 mL) until product starts to crystallize. Ether (100 mL) is added slowly to resulting slurry, in portions, and the mixture is stirred at ambient temperature for 2 h. Slightly gray crystals are filtered and washed with ethanol/ether (50:50) mixture to afford 22.2 g of compound VIII (49% over 3 steps). The purity is determined to be 97.9% by LC-MS. This batch is then recrystallized from methanol (150 mL) and ether (200 mL) to produce 19.3 g of VIII with 99% purity. 1H NMR (CD3OD) δ 8.01 (m, 2H), 7.30 (d, J=9 Hz, 1H), 7.08 (t, J=7.4 Hz, 1H), 6.82 (t, J=8.1 Hz, 1H), 6.63 (m, 2H), 4.30 (m, 4H), 4.10 (m, 1H), 3.80–2.90 (m, 9H), 1.55 (d, J=6.2 Hz, 3H). MP=245–248° C.

Workup

  1. temperatureThe resulting solution is refluxed for 18 h
  2. concentrationconcentrated in vacuum to a small volume (˜100 mL) until product
  3. customto crystallize
  4. additionEther (100 mL) is added slowly
  5. customto resulting slurry
  6. filtrationSlightly gray crystals are filtered
  7. washwashed with ethanol/ether (50:50) mixture

Sources & evidence

ORD record
ord-779b953e77fe402c909ac5a29593fac4
Source dataset
uspto-grants-2006_08
Patent number
US07091349B2

Reaction notes

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