Iodine → Hydroxy-di-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-yl ester

HRID 551372ノート

反応式

HRID 551372 の反応式
Br[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.[Mg].II.[CH3:10][N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18](=[O:26])[C:19](=[O:25])[C:20]2[S:21][CH:22]=[CH:23][CH:24]=2)[CH2:13][CH2:12]1.[Cl-].[NH4+]>C1COCC1>[CH3:10][N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18](=[O:26])[C:19]([OH:25])([C:20]2[S:21][CH:22]=[CH:23][CH:24]=2)[C:2]2[S:3][CH:4]=[CH:5][CH:6]=2)[CH2:13][CH2:12]1

参加物

7

反応物 5

HCID 807IodineHCID 138512-Bromothiophene2 回HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 67196156Oxo-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-yl ester

生成物 1

HCID 67195650Hydroxy-di-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-yl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
70 °C

実験手順

A solution of 2-bromothiophene (3.2 ml, 33 mmol) in THF (30 ml) is added dropwise to a mixture of magnesium (0.8 g, 33 mmol) and a single crystal of iodine in THF (30 ml). After addition of just under one half of the 2-bromothiophene the addition is suspended until reaction has initiated (judged by an exotherm). The addition is then completed maintaining the reaction temperature to below 40° C. After the addition is completed the reaction mixture is heated to 70° C. for 1 hour. This mixture is then cooled and added to a solution of oxo-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-yl ester (6.48 g, 25.6 mmol) in THF (80 ml). After the addition is completed the reaction mixture is stirred at room temperature for 1 hour and then heated to reflux for 2 hours. After cooling to room temperature saturated aqueous ammonium chloride solution (100 ml) is added. The solution is extracted with diethylether dried over magnesium sulphate, filtered and concentrated. Purification by flash silica column chromatography gives the title product.

後処理

  1. additionthe addition
  2. customis suspended until reaction
  3. additionThe addition
  4. temperatureis then completed maintaining the reaction temperature to below 40° C
  5. additionAfter the addition
  6. temperatureThis mixture is then cooled
  7. additionAfter the addition
  8. temperatureheated
  9. temperatureto reflux for 2 hours
  10. additionis added
  11. extractionThe solution is extracted with diethylether
  12. dry with materialdried over magnesium sulphate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customPurification by flash silica column chromatography

出典と根拠

ORDレコード
ord-3cc90eddb9b74cdd94f445bae2c1c953
出典データセット
uspto-grants-2011_05
特許番号
US07947730B2

反応ノート

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