4-(Chloromethyl)benzoyl chloride → HCID 59657777, compound

HRID 2055684Notes

Reaction equation

HRID 2055684 reaction equation
[CH2:1]([CH:3]([N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][C:13]([NH:15][OH:16])=[NH:14])[CH2:8][CH2:7]1)[CH2:4][CH3:5])[CH3:2].[Cl:17][CH2:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=O)=[CH:21][CH:20]=1>C(O)(=O)C>[Cl:17][CH2:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]2[O:16][N:15]=[C:13]([CH2:12][CH:9]3[CH2:10][CH2:11][N:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[CH2:7][CH2:8]3)[N:14]=2)=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 701364-(Chloromethyl)benzoyl chlorideHCID 178446096HCID 178446096, compound

Product 1

HCID 59657777HCID 59657777, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 2-((1-ethylpropyl)piperidin-4-yl)-N-hydroxyacetamidine (0.50 g, 2.2 mmol, prepared as described in Example 12), glacial acetic acid (15 mL) and 4-(chloromethyl)benzoyl chloride (0.46 g, 2.4 mmol) was stirred overnight at ambient temperature and then heated at reflux for 30 minutes. The mixture was concentrated in vacuo and the residue was dissolved in a mixture of 1 N hydrochloric acid (10 mL), water (50 mL) and diethyl ether (20 mL). The phases were separated and the aqueous phase was washed with diethyl ether (2×10 mL). The organic extracts were discarded and the aqueous phase was made alkaline (pH 10) with 4 N sodium hydroxide and then extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried (MgSO4) and the solvent was evaporated. This afforded 0.70 g of 4-[5-(4-(chloromethyl)phenyl)-[1,2,4]oxadiazol-3-ylmethyl]-1-(1-ethylpropyl)piperidine as an oil. 1H NMR (400 MHz, CDCl3) δ 0.87 (t, 6H), 1.22-1.49 (m, 4H), 1.40-1.52 (m, 2H), 1.67-1.74 (m, 2H), 1.78-1.88 (m, 1H), 2.13 (pent., 1H), 2.23-2.31 (m, 2H), 2.68-2.75 (m, 4H), 4.63 (s, 2H), 7.55 (d, 2H), 8.14 (d, 2H). HPLC: Rt=14.22 min.

Workup

  1. temperatureheated
  2. temperatureat reflux for 30 minutes
  3. concentrationThe mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in a mixture of 1 N hydrochloric acid (10 mL), water (50 mL) and diethyl ether (20 mL)
  5. customThe phases were separated
  6. washthe aqueous phase was washed with diethyl ether (2×10 mL)
  7. extractionextracted with ethyl acetate (2×50 mL)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-4cc156dfbb4d4ab49783fc2eb67e49ba
Source dataset
uspto-grants-2008_02
Patent number
US07332508B2

Reaction notes

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