Isobutyraldehyde → Methyl 2-(isobutylamino)thiophene-3-carboxylate

HRID 2104087

Reaction equation

HRID 2104087 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8].[CH:11](=O)[CH:12]([CH3:14])[CH3:13].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[CH2:11]([NH:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8])[CH:12]([CH3:14])[CH3:13]

Participants

6

Reactant 3

HCID 6561IsobutyraldehydeHCID 78381Methyl 2-amino-3-thenoateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 67317044Methyl 2-(isobutylamino)thiophene-3-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 2-aminothiophene-3-carboxylate (2.0 g, 12.7 mmol) in dichloromethane (40 mL) and glacial acetic acid (0.72 mL) were added isobutyraldehyde (0.87 g, 12.1 mmol) and sodium triacetoxyborohydride (4.0 g, 18.9 mmol). The reaction mixture was stirred for 18 h at room temperature and concentrated. The residue was dissolved in ethyl acetate, washed with aqueous sodium bicarbonate solution and with water, dried over anhydrous sodium sulfate and concentrated. The residual oil was purified on a silica gel flash chromatography column eluted with 5% ethyl acetate-hexane to afford the title compound as a slightly yellow oil (2.19 g, 81% yield). 1H NMR (400 MHz, CDCl3): δ 7.00 (d, 1H), 6.18 (d, 1H), 3.80 (s, 3H), 3.20 (m, 2H), 1.68 (m, 1H), 1.00 (d, 6H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with aqueous sodium bicarbonate solution and with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residual oil was purified on a silica gel flash chromatography column
  7. washeluted with 5% ethyl acetate-hexane

Sources & evidence

ORD record
ord-96af65fb2f2048049e951c853852fb92
Source dataset
uspto-grants-2009_08
Patent number
US07576211B2

Linked notes

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