Triethylamine → 3-{[3-(2-Chloro-6-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid methyl ester

HRID 2212181

Reaction equation

HRID 2212181 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:10]=1[C:16]1[C:20]([C:21](Cl)=[O:22])=[C:19]([CH3:24])[O:18][N:17]=1.[CH3:25][O:26][C:27]([N:29]1[CH2:34][CH2:33][CH2:32][CH:31]([NH2:35])[CH2:30]1)=[O:28]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:25][O:26][C:27]([N:29]1[CH2:34][CH2:33][CH2:32][CH:31]([NH:35][C:21]([C:20]2[C:16]([C:10]3[C:11]([F:15])=[CH:12][CH:13]=[CH:14][C:9]=3[Cl:8])=[N:17][O:18][C:19]=2[CH3:24])=[O:22])[CH2:30]1)=[O:28]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27365813-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chlorideHCID 222730981-Piperidinecarboxylicacid,3-amino-,methylester(9CI)

Product 1

HCID 696523893-{[3-(2-Chloro-6-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid methyl esterYield 90%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Add 4-dimethylamino-pyridine (0.19 g, 1.5 mmol), triethylamine (3.2 mL, 23.2 mmol), and 3-(2-chloro-6-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl chloride (5.53 g, 20.1 mmol) to a solution of 3-amino-piperidine-1-carboxylic acid methyl ester (2.45 g, 15.5 mmol) in dichloromethane (100 mL). Stir the reaction at room temperature under nitrogen overnight. Wash the reaction with 1N HCl, saturated aqueous sodium bicarbonate solution, and brine; dry over magnesium sulfate; and concentrate. Purify by flash chromatography on silica gel (eluting with 0.75% methanol/chloroform) to give 5.49 g of the title compound as a yellow foam, 90% yield. 1H NMR: consistent with structure. MS (ion spray) 396 (M+).

Workup

  1. customthe reaction at room temperature under nitrogen overnight
  2. washWash
  3. customthe reaction with 1N HCl, saturated aqueous sodium bicarbonate solution, and brine
  4. dry with materialdry over magnesium sulfate
  5. concentrationand concentrate
  6. customPurify by flash chromatography on silica gel (eluting with 0.75% methanol/chloroform)

Sources & evidence

ORD record
ord-4dc73491067f45c29621accb2f726714
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Linked notes

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