Ammonium Chloride → tert-Butyl [5-methoxy-2-(2-oxo-2-thiophen-3-ylethyl)phenyl]carbamate

HRID 2409942Notes

Reaction equation

HRID 2409942 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:17])=[C:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:8]=1.C([Li])(CC)C.CON(C)[C:26]([C:28]1[CH:32]=[CH:31][S:30][CH:29]=1)=[O:27].[Cl-].[NH4+]>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:17][C:26](=[O:27])[C:28]2[CH:32]=[CH:31][S:30][CH:29]=2)=[C:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[CH:8]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 10609920tert-Butyl (5-methoxy-2-methylphenyl)carbamateHCID 22489894N-methoxy-N-methylthiophene-3-carboxamideHCID 178418400CID 53628100

Product 1

HCID 69096725tert-Butyl [5-methoxy-2-(2-oxo-2-thiophen-3-ylethyl)phenyl]carbamateYield 63.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Under an argon atmosphere, to a solution of tert-butyl (5-methoxy-2-methylphenyl)carbamate (2.00 g) in tetrahydrofuran (38 mL) was added dropwise sec-butyllithium (1.00 mol/L hexane-cyclohexane solution, 18.5 mL) at −45° C., and this mixture was stirred for 30 minutes. Then, a solution of N-methoxy-N-methylthiophene-3-carboxamide (1.59 g) in tetrahydrofuran (4.1 mL) was added dropwise thereto, and this mixture was stirred at −45° C. for 30 minutes and at room temperature for additional 1 hour. To the reaction mixture were added a saturated aqueous ammonium chloride solution and water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (1.87 g). 1H-NMR (CDCl3) δ ppm: 1.53 (9H, s), 3.79 (3H, s), 4.08 (2H, s), 6.59 (1H, dd, J=2.8, 8.5 Hz), 7.08 (1H, d, J=8.5 Hz), 7.35 (1H, dd, J=2.8, 5.1 Hz), 7.43-7.56 (1H, br), 7.60 (1H, dd, J=1.3, 5.1 Hz), 7.80-8.10 (1H, br), 8.23 (1H, dd, J=1.3, 2.8 Hz).

Workup

  1. stirringthis mixture was stirred at −45° C. for 30 minutes and at room temperature for additional 1 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-e800b84ace824574a86907314f71147e
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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