Ammonium Chloride → tert-Butyl {5-methoxy-2-[2-(1-methylcyclopropyl)-2-oxoethyl]phenyl}carbamate

HRID 2409984Notes

Reaction equation

HRID 2409984 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([CH3:31])[CH2:30][CH2:29]1)=[O:27].[Cl-].[NH4+]>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:17][C:26]([C:28]2([CH3:31])[CH2:30][CH2:29]2)=[O:27])=[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 45084195HCID 45084195, compoundHCID 178418400CID 53628100

Product 1

HCID 86703301tert-Butyl {5-methoxy-2-[2-(1-methylcyclopropyl)-2-oxoethyl]phenyl}carbamateYield 65.8%

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 (42 mL) was slowly added dropwise sec-butyllithium (1.08 mol/L hexane-cyclohexane solution, 22 mL) at −45° C., and the mixture was stirred for 45 minutes. Then, a solution of N-methoxy-N,1-dimethylcyclopropane carboxamide (1.33 g) in tetrahydrofuran (4.2 mL) was added dropwise thereto, and the mixture was stirred at −45° C. for 45 minutes, and then stirred at room temperature for 3 hours. 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 magnesium 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 (1.77 g). 1H-NMR (CDCl3) δ ppm: 0.80-0.89 (2H, m), 1.35-1.44 (5H, m), 1.52 (9H, s), 3.55 (2H, s), 3.80 (3H, s), 6.57 (1H, dd, J=2.8, 8.3 Hz), 6.97 (1H, d, J=8.3 Hz), 7.46 (1H, br s), 7.90-8.28 (1H, br).

Workup

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

Sources & evidence

ORD record
ord-77a2c40d2a6a44fc84132e34116ec62e
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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