N-Methoxy-N-methylbenzamide → Tert-butyl[4-cyclopropyl-2-(2-oxo-2-phenylethyl)phenyl]carbamate

HRID 2400276Notes

Reaction equation

HRID 2400276 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[C:6]([CH3:18])[CH:5]=2)[CH2:3][CH2:2]1.C([Li])(CC)C.CON(C)[C:27](=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O1CCCC1>[C:13]([O:12][C:11](=[O:17])[NH:10][C:7]1[CH:8]=[CH:9][C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:5][C:6]=1[CH2:18][C:27](=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([CH3:14])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 569575N-Methoxy-N-methylbenzamideHCID 86665748tert-Butyl (4-cyclopropyl-2-methylphenyl)carbamateHCID 178418400CID 53628100

Product 1

HCID 131731722Tert-butyl[4-cyclopropyl-2-(2-oxo-2-phenylethyl)phenyl]carbamateYield 59.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an argon atmosphere, to a solution of tert-butyl (4-cyclopropyl-2-methylphenyl)carbamate (666 mg) in tetrahydrofuran (13.5 mL) was added dropwise sec-butyllithium (1.08 mol/L hexane-cyclohexane solution, 5.5 mL) at −45° C., and the mixture was stirred for 30 minutes. Next, a solution of N-methoxy-N-methylbenzamide (489 mg) in tetrahydrofuran (1.4 mL) was added dropwise thereto, and the mixture was stirred at −45° C. for 35 minutes and then stirred at room temperature for 2 more hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution/water (2/1, 30 mL), 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 (563 mg). 1H-NMR (CDCl3) δ ppm: 0.55-0.70 (2H, m), 0.80-1.00 (2H, m), 1.49 (9H, s), 1.75-1.90 (1H, m), 4.25 (2H, s), 6.85-7.00 (2H, m), 7.20-7.75 (5H, m), 8.00-8.15 (2H, m).

Workup

  1. stirringthe mixture was stirred at −45° C. for 35 minutes
  2. stirringstirred at room temperature for 2 more hours
  3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution/water (2/1, 30 mL)
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a62dadeac9ae46abac33b8c945071099
Source dataset
uspto-grants-2014_08
Patent number
US08796247B2

Reaction notes

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