Bromoacetonitrile → Methyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate

HRID 922578

反応式

HRID 922578 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]1(C)C=CC=CC=1.[Cl:18][C:19]1[N:24]=[C:23]([O:25][CH3:26])[C:22]([CH:27]([CH3:32])[C:28]([O:30][CH3:31])=[O:29])=[CH:21][CH:20]=1.BrC[C:35]#[N:36]>C1COCC1>[Cl:18][C:19]1[N:24]=[C:23]([O:25][CH3:26])[C:22]([C:27]([CH3:11])([CH2:32][C:35]#[N:36])[C:28]([O:30][CH3:31])=[O:29])=[CH:21][CH:20]=1

参加物

5

反応物 3

HCID 11534BromoacetonitrileHCID 86699379LiHMDS tolueneHCID 117992989Methyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate

生成物 1

HCID 117993231Methyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate収率 84.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

In a dry flask containing lithium bis(trimethylsilyl)amide/toluene (1.0 M, 13.1 mL, 13.1 mmol) and THF (18 mL) at −78° C. was added methyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate (2.39 g, 10.4 mmol) dropwise via syringe over 12 min resulting in a bright yellow solution. After 40 min, the resulting solution was added dropwise to a dry flask containing a solution of 2-bromoacetonitrile (1.38 mL, 20.8 mmol) in THF (18 mL) at 0° C. over 15 min, resulting in a color change from colorless to yellow to dark red-brown. Subsequent rinses with THF (2×1.5 mL) were cannulated over. After 50 min, the reaction was quenched with saturated aqueous ammonium chloride (18 mL). The mixture was diluted with heptanes (4× the reaction volume). The aqueous layer was extracted 2× with 1:1 EtOAc/heptanes (200 mL). The combined organic layers were dried over Na2SO4 and concentrated. Purification by silica gel column chromatography (220 g RediSep Gold column, 5-18% EtOAc/heptanes) provided methyl 2-(6-chloro-2-methoxypyridin-3-yl)-3-cyano-2-methylpropanoate (2.35 g, 84%) as a white solid. 1H NMR (600 MHz, CDCl3) δ: 1.74 (s, 3H), 3.07 (d, 1H), 3.14 (d, 1H), 3.67 (s, 3H), 3.95 (s, 3H), 7.00 (d, 1H), 7.57 (d, 1H); MS (AP+)(M+H) 269.

後処理

  1. customresulting in a bright yellow solution
  2. additionthe resulting solution was added dropwise to a dry flask
  3. customresulting in a color change from colorless to yellow to dark red-brown
  4. waitAfter 50 min
  5. customthe reaction was quenched with saturated aqueous ammonium chloride (18 mL)
  6. additionThe mixture was diluted with heptanes (4× the reaction volume)
  7. extractionThe aqueous layer was extracted 2× with 1:1 EtOAc/heptanes (200 mL)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. concentrationconcentrated
  10. customPurification by silica gel column chromatography (220 g RediSep Gold column, 5-18% EtOAc/heptanes)

出典と根拠

ORDレコード
ord-7be34606832445369bb97deb4f9931e2
出典データセット
uspto-grants-2016_03
特許番号
US09278953B2

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