Methyl iodide → 2-(5,7-Difluoro-quinolin-6-yl)-propionic acid methyl ester

HRID 456112ノート

反応式

HRID 456112 の反応式
[Li+].[CH3:2]C([N-]C(C)C)C.[CH3:9][O:10][C:11](=[O:25])[CH2:12][C:13]1[C:14]([F:24])=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[CH:18][CH:17]=[CH:16]2.CI>C1COCC1>[CH3:9][O:10][C:11](=[O:25])[CH:12]([C:13]1[C:14]([F:24])=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[CH:18][CH:17]=[CH:16]2)[CH3:2]

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 58190558Methyl 2-(5,7-difluoroquinolin-6-yl)acetate

生成物 1

HCID 581905742-(5,7-Difluoro-quinolin-6-yl)-propionic acid methyl ester収率 95.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of LDA (1.2 M in THF, 9.5 mL, 11.40 mmol) in dry THF (30 mL) at −78° C. was added dropwise a solution of (5,7-difluoroquinolin-6-yl)-acetic acid methyl ester (2.12 g, 9.50 mmol) in THF (20 mL). After 30 min, MeI (0.9 mL, 14.25 mmol) was added dropwise, and the reaction mixture was allowed to rise to 0° C. slowly. After 1 h, the reaction was quenched by satd. aq. NaHCO3 solution, and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, concentrated, and purified by flash chromatography to afford 2.272 g of the title compound as pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ ppm 8.93 (d, 1H), 8.39 (dd, 1H), 7.61 (dd, 1H), 7.41-7.46 (m, 1H), 4.29 (q, 1H), 3.73 (s, 3H), 1.62 (d, 3H). LCMS (method A): [MH]+=252, tR=5.09 min.

後処理

  1. customto rise to 0° C.
  2. waitAfter 1 h
  3. customthe reaction was quenched by satd
  4. extractionaq. NaHCO3 solution, and extracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash chromatography

出典と根拠

ORDレコード
ord-450b46fec419408aa8989414c7a77bb9
出典データセット
uspto-grants-2013_07
特許番号
US08497368B2

反応ノート

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