Acetic Acid → 5-[(3-Methoxy-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide

HRID 545482Notes

Reaction equation

HRID 545482 reaction equation
C(O[C:4]([C:6]1[S:10][C:9]2[CH:11]=[CH:12][C:13]([CH:15]=O)=[CH:14][C:8]=2[CH:7]=1)=[O:5])C.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][NH2:23].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C([O-])(O)=O.[Na+].Cl.[NH2:51][OH:52].C[O-].[Na+]>ClC(Cl)C>[OH:52][NH:51][C:4]([C:6]1[S:10][C:9]2[CH:11]=[CH:12][C:13]([CH2:15][NH:23][CH2:22][C:21]3[CH:24]=[CH:25][CH:26]=[C:19]([O:18][CH3:17])[CH:20]=3)=[CH:14][C:8]=2[CH:7]=1)=[O:5]

Participants

9

Reactant 7

HCID 176Acetic AcidHCID 211563-MethoxybenzylamineHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10942334Sodium MethoxideHCID 574439705-Formyl-benzo[b]thiophene-2-carboxylic acid ethyl ester

Product 1

HCID 589690465-[(3-Methoxy-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 5-formyl-benzo[b]thiophene-2-carboxylic acid ethyl ester (85 mg, 0.36 mmol) and 3-methoxy-benzylamine (60 μL, 0.46 mmol) in anhydrous dichloroethane (5 mL) were added sodium triacetoxyborohydride (230 mg, 1.08 mmol) and acetic acid (20 μL, 0.35 mmol). After the reaction was complete, 4 mL of saturated NaHCO3 was added. The organic was separated, washed with 4 mL of water and then concentrated. After drying under high vacuum, the residue was dissolved in anhydrous MeOH (5 mL) and hydroxylamine hydrochloride (95 mg, 1.37 mmol) was added, followed by the addition of NaOMe solution (4.37 M in MeOH, 0.60 mL, 2.6 mmol). The mixture was allowed to stir at rt till the reaction was complete. The reaction mixture was concentrated and the residue was dissolved in a minimal amount of water. The obtained solution was acidified with 2N HCl to pH≈8. The solid formed was filtered, washed with water, collected and purified by flash column chromatography to give 5-[(3-methoxy-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide as a yellowish syrup. 1H NMR (DMSO-d6, 200 MHz) δ 7.94 (d, J=8.4 Hz, 1H), 7.88 (s, 1H), 7.85 (s, 1H), 7.44 (dd, J=8.4, 1.4 Hz, 1H), 7.21 (t, J=7.6 Hz, 1H), 7.00-6.72 (m, 3H), 3.78 (s, 2H), 3.73 (s, 3H), 3.66 (s, 2H). MS (EI): cal'd 343.1 (MH+), exp 343.2 (MH+).

Workup

  1. customThe organic was separated
  2. washwashed with 4 mL of water
  3. concentrationconcentrated
  4. customAfter drying under high vacuum
  5. dissolutionthe residue was dissolved in anhydrous MeOH (5 mL)
  6. concentrationThe reaction mixture was concentrated
  7. dissolutionthe residue was dissolved in a minimal amount of water
  8. customThe solid formed
  9. filtrationwas filtered
  10. washwashed with water
  11. customcollected
  12. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-2b8137e10c0f4b2e857d4d9b04964b7e
Source dataset
uspto-grants-2011_05
Patent number
US07935724B2

Reaction notes

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