2-Methoxyaniline → HCID 10547933, compound

HRID 964001Notes

Reaction equation

HRID 964001 reaction equation
ClC(OCC)=O.[O:7]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][CH2:9][CH:8]1[CH2:17][N:18]1[CH2:23][CH2:22][CH:21]([C:24]([OH:26])=O)[CH2:20][CH2:19]1.C(N(CC)CC)C.[CH3:34][O:35][C:36]1[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=1[NH2:38]>C(Cl)(Cl)Cl>[O:7]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][CH2:9][CH:8]1[CH2:17][N:18]1[CH2:19][CH2:20][CH:21]([C:24]([NH:38][C:37]2[CH:39]=[CH:40][CH:41]=[CH:42][C:36]=2[O:35][CH3:34])=[O:26])[CH2:22][CH2:23]1

Participants

6

Reactant 4

HCID 70002-MethoxyanilineHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 10564475HCID 10564475, compound

Product 1

HCID 10547933HCID 10547933, compoundYield 13.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

Ethyl chloroformate (0.1 g) was added dropwise to a stirred solution of 1-(1,4-benzodioxan-2-ylmethyl)piperidine-4-carboxylic acid (0.28 g) and triethylamine (0.12 g) in chloroform (10 ml) at 0° C. After 30 minutes a solution of 2-methoxyaniline (0.12 g) in chloroform (5 ml) was added and the mixture stirred at ambient temperature for 16 hours. The reaction mixture was then washed sequentially with water, aqueous sodium hydroxide solution (1M), hydrochloric acid (1M) and water. The solution was dried over magnesium sulphate, the solvent was removed in vacuo, and the residue was eluted through a silica column using a 1:1 mixture of petroleum ether (b.p. 40°-60° C.) and ethyl acetate as eluant. The solvent was removed in vacuo to yield 1-(1,4-benzodioxan-2-ylmethyl)-N-(2-methoxyphenyl)piperidine-4-carboxamide as a solid (50 mg). This procedure was repeated on 9X scale with the following changes. The reaction was heated to 50° C. for 1 hour after being stirred at ambient temperature for 16 hours. The solvent was then removed in vacuo and the residue was eluted through a silica column as previously described. Further desired product (1.05 g) was obtained.

Workup

  1. washThe reaction mixture was then washed sequentially with water, aqueous sodium hydroxide solution (1M), hydrochloric acid (1M) and water
  2. dry with materialThe solution was dried over magnesium sulphate
  3. customthe solvent was removed in vacuo
  4. washthe residue was eluted through a silica column
  5. additiona 1:1 mixture of petroleum ether (b.p. 40°-60° C.) and ethyl acetate as eluant
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-e060004f7a29444a9ff10a597761dc92
Source dataset
uspto-grants-1998_06
Patent number
US05767116

Reaction notes

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