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

HRID 1710552Notes

Reaction equation

HRID 1710552 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 (4.3 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-f418c8c904604d93b53c625fe4a4324f
Source dataset
uspto-grants-2010_09
Patent number
US07790716B2

Reaction notes

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