Acetic Anhydride → HCID 11473695, compound

HRID 545490Notes

Reaction equation

HRID 545490 reaction equation
C(O[C:4]([C:6]1[S:10]C2C=[C:12]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:13]=[CH:14][C:8]=2[C:7]=1[CH3:23])=O)C.CN1CCOCC1.C(O[C:35](=[O:37])[CH3:36])(=O)C.[C:38]([O-:41])(O)=O.[Na+].Cl.[NH2:44][OH:45].[CH3:46][O-].[Na+]>CN(C1C=CN=CC=1)C.ClCCl>[OH:45][NH:44][C:35]([C:36]1[S:10][C:6]2[CH:4]=[C:13]([CH2:12][N:15]([C:38](=[O:41])[CH3:46])[CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:14]=[CH:8][C:7]=2[CH:23]=1)=[O:37]

Participants

9

Reactant 6

HCID 7918Acetic AnhydrideHCID 79724-MethylmorpholineHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 10942334Sodium MethoxideHCID 67200299HCID 67200299, compound

Product 1

HCID 11473695HCID 11473695, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(benzylamino)-methyl-benzo[b]thiophene-2-carboxylic acid ethyl ester (112 mg, 0.34 mmol), NMM (0.12 mL, 1.09 mmol) and DMAP (10 mg, 0.08 mmol) in anhydrous dichloromethane (5 mL) at 0° C. was added acetic anhydride (48 μL, 0.51 mmol). The reaction mixture was allowed to warm to rt. After the reaction was complete, 5 mL of saturated NaHCO3 was added. The organic layer was separated, washed with 5 mL of water and then concentrated. After drying under high vacuum, the residue was dissolved in anhydrous MeOH (6 mL) and hydroxylamine hydrochloride (90 mg, 1.30 mmol) was added, followed by the addition of NaOMe solution (4.37 M in MeOH, 0.57 mL, 2.5 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 6-[(acetyl-benzyl-amino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide as a pale solid (83.3 mg, 69%). 1H NMR (DMSO-d6, 200 MHz) δ 11.47 (brs, 1H), 9.30 (brs, 1H), 7.98-7.74 (m, 3H), 7.44-7.10 (m, 6H), 4.65-4.40 (m, 4H), 2.12 (s, 3H). MS (EI): cal'd 355.1 (MH+), exp 355.2 (MH+).

Workup

  1. customThe organic layer was separated
  2. washwashed with 5 mL of water
  3. concentrationconcentrated
  4. customAfter drying under high vacuum
  5. dissolutionthe residue was dissolved in anhydrous MeOH (6 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-fd660dc3438142429115dc7c8715b5db
Source dataset
uspto-grants-2011_05
Patent number
US07935724B2

Reaction notes

Loading…