Sodium Hydroxide → 6-(2,6-Difluorophenyl)pyridine-3-carboxylic acid

HRID 915636ノート

反応式

HRID 915636 の反応式
C([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[F:19])=[CH:10][CH:11]=1)=[O:5])C.[OH-].[Na+]>CO>[F:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([F:18])[C:12]=1[C:9]1[N:8]=[CH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:11][CH:10]=1

参加物

4

反応物 2

HCID 14798Sodium HydroxideHCID 69129633Ethyl 6-(2,6-difluorophenyl)-3-pyridinecarboxylate

生成物 1

HCID 532230666-(2,6-Difluorophenyl)pyridine-3-carboxylic acid収率 63%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

Combine the mixture as obtained above (0.225 g, 1.04 mmol) with hexamethylditin (0.375 g, 1.15 mmol), Pd(OAc)2 (21 mg, 0.09 mmol), and triphenylphosphine (25 mg, 0.09 mmol) in toluene (5 mL). Purge with N2 and stir at 80° C. for 18 hours. Cool reaction to room temperature. Add a solution of 1-bromo-2,6-difluorobenzene (250 mg, 1.29 mmol) in toluene (1 mL) followed by Pd(OAc)2 (21 mg, 0.09 mmol) and triphenylphosphine (25 mg, 0.09 mmol). Purge with N2 and stir at 80° C. for an additional 18 hours. Cool reaction to room temperature. Evaporate the solvent and purify by column chromatography (silica, 10% ethyl acetate in hexane) to give 50 mg (20% yield) of 6-(2,6-difluorophenyl)pyridine-3-carboxylic acid ethyl ester. Hydrolyze the ester with 1 N sodium hydroxide solution (0.22 mL, 0.22 mmol) in methanol (3 mL) at room temperature for 3 days. Remove the volatiles under vacuum and combine the residue with 1 N hydrochloric acid solution. Collect the white solid by filtration, wash with water, and dry under vacuum to give 30 mg (63% yield) of the title compound. MS (m/e): 235.9 (MH+).

後処理

  1. customat room temperature
  2. customfor 3 days
  3. customRemove the volatiles under vacuum
  4. customCollect the white solid
  5. filtrationby filtration
  6. washwash with water
  7. customdry under vacuum

出典と根拠

ORDレコード
ord-a7f94711b9964241a6758d92de90823c
出典データセット
uspto-grants-2007_09
特許番号
US07265246B2

反応ノート

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