Triethylamine → 2-Chlorobenzenesulfonic acid 3-[(1-acetimidoylpiperidin-4-yl)methoxy]-5-methylphenyl ester hydrochloride

HRID 368522Notes

Reaction equation

HRID 368522 reaction equation
[CH2:1]([N:3](CC)CC)[CH3:2].Cl.C(=N)(OCC)C.[NH:15]1[CH2:20][CH2:19][CH:18]([CH2:21][O:22][C:23]2[CH:24]=[C:25]([O:30][S:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[Cl:40])(=[O:33])=[O:32])[CH:26]=[C:27]([CH3:29])[CH:28]=2)[CH2:17][CH2:16]1>CN(C)C=O>[ClH:40].[C:1]([N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][O:22][C:23]2[CH:24]=[C:25]([O:30][S:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[Cl:40])(=[O:32])=[O:33])[CH:26]=[C:27]([CH3:29])[CH:28]=2)[CH2:17][CH2:16]1)(=[NH:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 158950942-Chlorobenzenesulfonic acid 3-[(piperidin-4-yl)methoxy]-5-methylphenyl ester

Product 1

HCID 867552112-Chlorobenzenesulfonic acid 3-[(1-acetimidoylpiperidin-4-yl)methoxy]-5-methylphenyl ester hydrochlorideYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Triethylamine (0.5 mL) and ethyl acetimidate hydrochloride (247 mg, 2.0 mmol) were added to a solution of 2-chlorobenzenesulfonic acid 3-[(piperidin-4-yl)methoxy]-5-methylphenyl ester (396 mg, 1.0 mmol), as prepared in the preceding step, in N,N-dimethylformamide (10 mL). The reaction mixture was stirred at room temperature overnight. The N,N-dimethylformamide was removed in vacuo and the residue partitioned between methylene chloride (200 mL) and 10% K2CO3 (50 mL). The organic phase was washed with 10% K2CO3 (2×50 mL) and dried over K2CO3. The solvent was removed in vacuo, HCl-methanol (30 mL) was added, and the solution was concentrated in vacuo. The residue was crystallized from methanol-ethyl acetate to give the title compound as white crystals (405 mg, 86%). 1H-NMR (300 MHz, DMSO-d6) δ 1.30 (m, 2 H), 1.82 (d, 2 H, J=7.0 Hz), 2.05 (m, 1 H), 2.20 (s, 3 H), 2.29 (s, 3 H), 3.16 (m, 2 H), 3.77 (d, 2 H, J=3.0 Hz), 3.92 (d, 1 H, J=6.5 Hz), 4.17 (d, 1 H, J=6.5 Hz), 6.46 (d, 1 H, J=2.5 Hz), 6.49 (s, 1 H), 7.59 (t, 1 H. J=8.0 Hz), 7.87 (m, 2 H), 7.95 (d, 1 H, J=8.0 Hz), 8.77 (br s, 1 H), and 9.35 (br s, 1 H). Mass spectrum (MALDI-TOF, sinapinic acid matrix) calcd. for C21H25N2O4SCl: 437.1 (M+H). Found: 436.8.

Workup

  1. customThe N,N-dimethylformamide was removed in vacuo
  2. customthe residue partitioned between methylene chloride (200 mL) and 10% K2CO3 (50 mL)
  3. washThe organic phase was washed with 10% K2CO3 (2×50 mL)
  4. dry with materialdried over K2CO3
  5. customThe solvent was removed in vacuo, HCl-methanol (30 mL)
  6. additionwas added
  7. concentrationthe solution was concentrated in vacuo
  8. customThe residue was crystallized from methanol-ethyl acetate

Sources & evidence

ORD record
ord-cfcb1ea7af0e4f08b4a1adfe83c08f05
Source dataset
uspto-grants-2000_10
Patent number
US06133315

Reaction notes

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