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

HRID 551375Notes

Reaction equation

HRID 551375 reaction equation
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]([CH2:17][O:18][C:19](=[O:27])[C:20](=[O:26])[C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)[CH2:13][CH2:12]1.[Cl-].[NH4+]>C1COCC1.C(OCC)C>[CH3:10][N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][O:18][C:19](=[O:27])[C:20]([OH:26])([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)[C:2]2[S:3][CH:4]=[CH:5][CH:6]=2)[CH2:13][CH2:12]1

Participants

8

Reactant 5

HCID 807IodineHCID 138512-Bromothiophene2×HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 67197151Oxo-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-ylmethyl ester

Product 1

HCID 67198340Hydroxy-di-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 2-bromothiophene (2.15 ml, 22.2 mmol) in THF (15 ml) is added dropwise to a mixture of magnesium (0.54 g, 22.2 mmol) and a single crystal of iodine in THF (15 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 reflux for 20 minutes. This mixture is then cooled and added to a solution of oxo-thiophen-2-yl-acetic acid 1-methyl-piperidin-4-ylmethyl ester (4.6 g, 17.2 mmol) in THF (40 ml). After the addition is completed the reaction mixture is stirred at room temperature for 1 hour and then heated to reflux for 2.5 hours. After cooling to room temperature saturated aqueous ammonium chloride solution (100 ml) is added together with diethylether. The solution is extracted with diethylether dried over magnesium sulphate, filtered and concentrated. Purification by flash silica column chromatography gives the title product.

Workup

  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. temperatureis heated
  7. temperatureto reflux for 20 minutes
  8. temperatureThis mixture is then cooled
  9. additionAfter the addition
  10. temperatureheated
  11. temperatureto reflux for 2.5 hours
  12. extractionThe solution is extracted with diethylether
  13. dry with materialdried over magnesium sulphate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customPurification by flash silica column chromatography

Sources & evidence

ORD record
ord-2dc5cd17fa8442369188dfb862bef6cc
Source dataset
uspto-grants-2011_05
Patent number
US07947730B2

Reaction notes

Loading…