Iodoethane → Methyl 2-[4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]-2-ethoxyacetate

HRID 1627895Notes

Reaction equation

HRID 1627895 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]([OH:13])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:14])[N:5]=[C:4]2[S:15][C:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[C:3]=12.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:33][CH3:34]>CN(C=O)C>[Cl:1][C:2]1[C:7]([CH:8]([O:13][CH2:33][CH3:34])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:14])[N:5]=[C:4]2[S:15][C:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[C:3]=12

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 2733832Lithium HexamethyldisilazideHCID 66603831Methyl 2-[4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]-2-hydroxyacetate

Product 1

HCID 66603554Methyl 2-[4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]-2-ethoxyacetateYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-15 °C

Procedure

To a cold solution of methyl 2-[4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]-2-hydroxyacetate (0.100 g; 0.307 mmol) in dry DMF (1.5 ml) at −15° C. under nitrogen atmosphere was added LHMDS (1M in THF) (0.338 mL; 0.338 mmol) dropwise and the mixture was stirred at −15° C. for 15 min. Then, iodoethane (0.049 mL; 0.614 mmol) was added and the mixture was allowed to warm up to room temperature. After 72 h, the reaction was quenched by adding a saturated solution of ammonium chloride, extracted with dichloromethane and the combined organics were washed with brine, dried over magnesium sulphate and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethylacetate (5-40%) in heptane furnished 0.040 g (37%) of the title compound as a solid.

Workup

  1. temperatureto warm up to room temperature
  2. waitAfter 72 h
  3. customthe reaction was quenched
  4. additionby adding a saturated solution of ammonium chloride
  5. extractionextracted with dichloromethane
  6. washthe combined organics were washed with brine
  7. dry with materialdried over magnesium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash chromatography on silica gel using a gradient of ethylacetate (5-40%) in heptane

Sources & evidence

ORD record
ord-68e2989098aa4fc7b20bcf347d344526
Source dataset
uspto-grants-2014_07
Patent number
US08785638B2

Reaction notes

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