Triethylamine → (3,5-Difluoropyridin-2-yl)(3-fluoroazetidin-1-yl)methanone

HRID 1643854ノート

反応式

HRID 1643854 の反応式
[F:1][C:2]1[C:3]([C:9]([OH:11])=O)=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.[F:12][CH:13]1[CH2:16][NH:15][CH2:14]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:1][C:2]1[C:3]([C:9]([N:15]2[CH2:16][CH:13]([F:12])[CH2:14]2)=[O:11])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 27832623,5-Difluoropyridine-2-carboxylic acidHCID 36035423-FluoroazetidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

生成物 1

HCID 59559983(3,5-Difluoropyridin-2-yl)(3-fluoroazetidin-1-yl)methanone収率 51.6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 3,5-difluoropicolinic acid (16.40 g, 103.1 mmol), 3-fluoroazetidine (8.59 g, 114 mmol) and triethylamine (27.70 ml, 199.0 mmol) in 100 mL of DMF was added HATU (45.40 g, 119.0 mmol). The mixture was stirred at room temperature for 3 hr, quenched with water, extracted with 3× EtOAc. The combined organic layer was washed with 2×H2O, dried with Na2SO4, and concentrated to provide an oil that was purified by Biotage eluting with 25-40% EtOAc in hexanes to give a yellow solid (11.49 g, 46.3% yield). 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J=2.53 Hz, 1 H) 7.31-7.46 (m, 1 H) 5.27-5.52 (m, 1 H) 4.62-4.79 (m, 1 H) 4.42-4.59 (m, 2 H) 4.22-4.38 (m, 1 H); MS for C9H7F3N2O m/z 217.00 (M+H)+

後処理

  1. customquenched with water
  2. extractionextracted with 3× EtOAc
  3. washThe combined organic layer was washed with 2×H2O
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated
  6. customto provide an oil that
  7. customwas purified by Biotage
  8. washeluting with 25-40% EtOAc in hexanes

出典と根拠

ORDレコード
ord-73abee3335724341963a685febbb6a96
出典データセット
uspto-grants-2012_02
特許番号
US08119624B2

反応ノート

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