Methyl chloroglyoxylate → HCID 59408989、化合物

HRID 1894732ノート

反応式

HRID 1894732 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9]3=[C:10]([CH2:12][CH2:13][N:8]3[CH2:7][CH2:6][CH2:5]2)[CH:11]=1.C([Li])CCC.[Cu]C#N.Cl[C:23](=[O:28])[C:24]([O:26][CH3:27])=[O:25].C(=O)(O)[O-].[Na+]>O1CCCC1.ClCCl.O>[CH3:27][O:26][C:24](=[O:25])[C:23](=[O:28])[C:2]1[CH:3]=[C:4]2[C:9]3=[C:10]([CH2:12][CH2:13][N:8]3[CH2:7][CH2:6][CH2:5]2)[CH:11]=1

参加物

9

反応物 5

HCID 79846Methyl chloroglyoxylateHCID 516892Sodium BicarbonateHCID 59409002HCID 59409002、化合物HCID 178418339ButyllithiumHCID 178418546HCID 178418546、化合物

生成物 1

HCID 59408989HCID 59408989、化合物収率 85.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A solution 8-bromo-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline (9.53 g, 40.0 mmol) in anhydrous tetrahydrofuran (317 ml) cooled to −78° C. was treated with n-butyllithium (36.1 ml, 90.1 mmol; 2.5M solution in hexanes) then stirred for 20 minutes. The reaction was treated with copper (I) cyanide (10.88 g, 120.1 mmol) then allowed to warm to between 0 and 10° C. before cooling back to −78° C. Methyl chlorooxoacetate (11.1 ml, 120.7 mmol) was added and the mixture was allowed to warm to room temperature. Water (250 ml) was added to the reaction and then the reaction was basified with saturated aqueous sodium bicarbonate. Dichloromethane (200 ml) was added and the mixture was filtered through a bed of celite. The organic layer was removed and the aqueous layer was extracted with dichloromethane (2×200 ml). The combined organic layers were dried with anhydrous sodium sulfate and evaporated to dryness to give a dark green oil which was purified by flash column chromatography (SiO2, 20% EtOAc in hexanes to 25% EtOAc in hexanes) to afford oxo-(1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-acetic acid methyl ester as a yellow/brown solid (8.4 g). M.p=102-105° C.; 400 MHz 1H NMR (CDCl3) δ: 7.55 (s, 1H), 7.50 (s, 1H), 3.92 (s, 3H), 3.58 (t, 2H), 3.19 (m, 2H), 3.01 (t, 2H), 2.66 (t, 2H), 2.02 (m, 2H); LCMS: 246 [M+H].

後処理

  1. temperatureto warm to between 0 and 10° C.
  2. temperatureto warm to room temperature
  3. filtrationthe mixture was filtered through a bed of celite
  4. customThe organic layer was removed
  5. extractionthe aqueous layer was extracted with dichloromethane (2×200 ml)
  6. dry with materialThe combined organic layers were dried with anhydrous sodium sulfate
  7. customevaporated to dryness
  8. customto give a dark green oil which
  9. customwas purified by flash column chromatography (SiO2, 20% EtOAc in hexanes to 25% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-7c44f1b7012849e989c7acb3dde27691
出典データセット
uspto-grants-2013_08
特許番号
US08513292B2

反応ノート

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