Hydrochloric Acid → HCID 17836479, compound

HRID 348510Notes

Reaction equation

HRID 348510 reaction equation
[C:1]([C:3]1[C:4]2[C:11]([CH3:12])=[CH:10][CH:9]=[CH:8][C:5]=2[S:6][CH:7]=1)#[N:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.[OH-].[Na+]>C(OCC)C.C1COCC1>[NH2:2][CH2:1][C:3]1[C:4]2[C:11]([CH3:12])=[CH:10][CH:9]=[CH:8][C:5]=2[S:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 17836484HCID 17836484, compoundHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 17836479HCID 17836479, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

After dropping a diethyl ether (20 ml) and THF (20 ml) solution containing 9.10 g (52.6 mmol) of the 3-cyano-4-methylbenzo[b]thiophene obtained in Step 4 into 50 ml of a diethyl ether suspension of 2.0 g (53 mmol) of lithium aluminum hydride over the course of 15 minutes at 0° C., the solution was stirred for 30 minutes at room temperature. Following completion of the reaction, excess LAH in the reaction solution was treated with hydrochloric acid followed by the addition of aqueous sodium hydroxide solution to make alkaline. After saturating the aqueous phase with potassium carbonate, extracting with dichloromethane and washing the organic phase with water, it was dried with magnesium sulfate. The solvent was then concentrated under reduced pressure to obtain 3-aminomethyl-4-methylbenzo[b]thiophene. 11.5 (250 mmol) of formic acid and 10.0 g (123 mmol) of 37% aqueous formaldehyde solution were sequentially added to this followed by stirring for 5 hours at 80° C. Following completion of the reaction, after adding aqueous hydrochloric acid solution to the reaction solution, it was concentrated under reduced pressure to remove the formic acid and formaldehyde. Aqueous sodium hydroxide solution was then added to make the solution alkaline followed by extraction with dichloromethane. After washing the organic phase with water, it was dried with magnesium sulfate and the solvent was concentrated under reduced pressure. The residue was then purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain 2.61 g (12.8 mmol) of the target compound (yield of the two steps: 24%). Confirmation of the compound was carried out by identifying from 1H-NMR.

Workup

  1. concentrationAfter saturating the aqueous phase with potassium carbonate
  2. extractionextracting with dichloromethane
  3. washwashing the organic phase with water, it
  4. dry with materialwas dried with magnesium sulfate
  5. concentrationThe solvent was then concentrated under reduced pressure

Sources & evidence

ORD record
ord-4926ce2f000d48f9b76b5d43a99584d3
Source dataset
uspto-grants-2007_02
Patent number
US07176320B2

Reaction notes

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