Sodium hydride → 6-(Cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)picolinic acid

HRID 927462ノート

反応式

HRID 927462 の反応式
[H-].[Na+].[CH:3]1([CH2:6][OH:7])[CH2:5][CH2:4]1.C[O:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:21][C:20]([F:23])([F:22])[CH2:19]2)=[C:14](Cl)[N:13]=1)=[O:11]>CN(C=O)C>[CH:3]1([CH2:6][O:7][C:14]2[N:13]=[C:12]([C:10]([OH:11])=[O:9])[CH:17]=[CH:16][C:15]=2[N:18]2[CH2:21][C:20]([F:23])([F:22])[CH2:19]2)[CH2:5][CH2:4]1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 75644CyclopropanemethanolHCID 866747536-Chloro-5-(3,3-difluoroazetidin-1-yl)-pyridine-2-carboxylic acid methyl ester

生成物 1

HCID 710872926-(Cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)picolinic acid収率 14.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Sodium hydride (0.29 g, 8.4 mmol) was added in portion to a solution of cyclopropylmethanol (CAN 2516-33-8, 0.36 g, 5 mmol) in DMF (3 mL) and the mixture was stirred at room temperature for 2 h. 6-Chloro-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid methyl ester (0.44 g, 1.68 mmol) was added to the mixture and the resulting solution was stirred at 110° C. overnight. After concentration, water (20 mL) was added to the residue and the solution was acidified with an aqueous solution of hydrochloride (6 N), then extracted with ethyl acetate (2×20 mL). The combined organic phase was washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give a residue. The residue was purified by prep-TLC (eluting with 50% ethyl acetate in petroleum ether) to give the target compound (0.07 g, 14%); MS (EI): m/e=285.1 [M+H]+.

後処理

  1. stirringthe resulting solution was stirred at 110° C. overnight
  2. concentrationAfter concentration, water (20 mL)
  3. additionwas added to the residue
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. washThe combined organic phase was washed with brine (20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a residue
  10. customThe residue was purified by prep-TLC (eluting with 50% ethyl acetate in petroleum ether)

出典と根拠

ORDレコード
ord-ea14b0fa8f2c45b690377f7d15090be8
出典データセット
uspto-grants-2016_03
特許番号
US09290451B2

反応ノート

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