Acetic Acid → N-methyl-benzo[b]thiophene-3-methanamine

HRID 2112684Notes

Reaction equation

HRID 2112684 reaction equation
[CH3:1][NH2:2].CO.[S:5]1[CH:9]=[C:8]([CH:10]=O)[C:7]2[CH:12]=[CH:13][CH:14]=[CH:15][C:6]1=2.CC(O)=O>>[CH3:1][NH:2][CH2:10][C:8]1[C:7]2[CH:12]=[CH:13][CH:14]=[CH:15][C:6]=2[S:5][CH:9]=1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 6329MethylamineHCID 2273281-Benzothiophene-3-carbaldehyde

Product 1

HCID 13576467N-methyl-benzo[b]thiophene-3-methanamineYield 48%

Procedure

To a stirred solution of 2 M methylamine in methanol (75 mmole, 150 mmole) was added benzo[b]thiophen-3-carboxaldehyde (5.3 g, 33 mmole) and HOAc (43 mL, 75 mmole). The reaction was stirred at RT for 1 h, then NaB3CN (2.1 g, 33 mmole) was added portionwise over 5 minutes. The reaction was stirred for an additional 16 h then was concentrated under vacuum. The residue was taken up in Et2O (300 mL) and washed with 1.0 N NaOH (300 mL) then with brine, dried (Na2SO4), and concentrated. Purification by flash chromatography on silica gel (5% (5% NH4OH/MeOH)/CHCl3) gave the title compound (2.81 g, 48%) as a brownish oil: 1H NMR (400 MHz, CDCl3) δ 7.87 (2d, 2H), 7.40 (m, 2H), 7.32 (s, 1H), 4.02 (s, 2H), 2.56 (s, 3H), 1.5 (br s, 1H).

Workup

  1. stirringThe reaction was stirred for an additional 16 h
  2. concentrationthen was concentrated under vacuum
  3. washwashed with 1.0 N NaOH (300 mL)
  4. dry with materialwith brine, dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica gel (5% (5% NH4OH/MeOH)/CHCl3)

Sources & evidence

ORD record
ord-3cd4ea387a1a4d74bb9aca835d18db1d
Source dataset
uspto-grants-2009_04
Patent number
US07524843B2

Reaction notes

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