Tributyltin Chloride → 4-chloro-3-(4-fluoro-phenyl)-5-tributylstannanyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1693726ノート

反応式

HRID 1693726 の反応式
Br[C:2]1[C:3]([Cl:26])=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[Cl-].[Li+].C([Mg]Cl)(C)C.[CH2:34]([Sn:38](Cl)([CH2:43][CH2:44][CH2:45][CH3:46])[CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH3:37].[Cl-].[NH4+]>C1COCC1.C(OCC)C>[Cl:26][C:3]1[C:2]([Sn:38]([CH2:39][CH2:40][CH2:41][CH3:42])([CH2:43][CH2:44][CH2:45][CH3:46])[CH2:34][CH2:35][CH2:36][CH3:37])=[CH:7][N:6]=[C:5]2[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:4]=12

参加物

8

反応物 5

HCID 15096Tributyltin ChlorideHCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 575374765-bromo-4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918、化合物

生成物 1

HCID 575376414-chloro-3-(4-fluoro-phenyl)-5-tributylstannanyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine収率 121.1%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-25 °C

実験手順

1.30 g (2.85 mmol) of 5-bromo-4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine and 750 mg (17.69 mmol) of anhydrous vacuum dried lithium chloride were dissolved under nitrogen in 50 mL of anhydrous THF. The resulting solution was cooled to −25° C. and 2.0 mL (4 mmol) of a 2 M solution of iso-propyl-magnesium chloride in anhydrous THF was added dropwise. The resulting mixture was allowed to stir at −25 to −5° C. for 2 h. 2.0 mL (7.4 mmol) of tri-n-butyltin chloride was added slowly to the resulting mixture. Upon complete addition the reaction mixture was allowed to stir for 18 h, allowing to warm to ambient temperature. The resulting reaction mixture was distributed between diethyl ether and a saturated aqueous solution of ammonium chloride. The aqueous phase was separated and extracted twice with diethyl ether. The combined organic phases were dried over sodium sulfate and evaporated. The residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes to afford 2.298 g (3.45 mmol, 121%) of 4-chloro-3-(4-fluoro-phenyl)-5-tributylstannanyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine as a colorless oil. 1H-NMR [500 MHz, d6-DMSO] δ: 8.13 (s, 1H), 7.77 (s, 1H), 7.49-7.45 (m, 2H), 7.27-7.22 (m, 2H), 5.66 (s, 2H), 3.55 (t, 2H), 1.63-1.47* (m, 6H), 1.34-1.08* (m, 12H), 0.89-0.80* (t, 9H), −0.12 (s, 9H) [*: compound contaminated with other tri-n-butyl tin side product(s) in shift ranges indicated, appearing as distinct sets of peaks with equal integration to desired product]; MS [MH+] m/z: 665+667.

後処理

  1. additionUpon complete addition the reaction mixture
  2. stirringto stir for 18 h
  3. temperatureto warm to ambient temperature
  4. customThe resulting reaction mixture
  5. customThe aqueous phase was separated
  6. extractionextracted twice with diethyl ether
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. customevaporated
  9. customThe residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes

出典と根拠

ORDレコード
ord-9ef78ddd5edb4679bbaba660a9bd4b14
出典データセット
uspto-grants-2012_04
特許番号
US08158647B2

反応ノート

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