Acetonitrile → (3-Cyclopentyloxy-4-methoxy-phenyl)-phenyl-methanone

HRID 583478Notes

Reaction equation

HRID 583478 reaction equation
CON(C)[C:4](=[O:19])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[CH:6]=1.[C:21]1([Mg]Br)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CC#N>CCOCC>[CH:14]1([O:13][C:7]2[CH:6]=[C:5]([CH:10]=[CH:9][C:8]=2[O:11][CH3:12])[C:4]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:19])[CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 21187934HCID 21187934, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 10827779(3-Cyclopentyloxy-4-methoxy-phenyl)-phenyl-methanone

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To an ice bath cooled stirred solution of N-methoxy-N-methyl-3-cyclopentoxy-4-methoxybenzamide (1.2 g, 4.3 mmol) in 15 mL of anhydrous ether was added a 3 M solution of phenylmagnesium bromide (3.6 mL, 10.8 mmol) in ether dropwise over a 20 minute period. A white gum precipitated from the mixture and dry THF (6 mL) was added to facilitate stirring. The reaction mixture was allowed to warm to room temperature and was stirred for 4 hours. The reaction was then quenched at 0° C. with a saturated aqueous solution of ammonium chloride (8 mL). The resulting mixture was allowed to warm to room temperature and was diluted with ethyl acetate (10 mL). The organic layer was separated and sequentially washed with 1 N citric acid (2×10 mL), saturated NaHCO3(aq) (2×10 mL), and brine (2×10 mL). The organic layer was then dried over MgSO4, filtered and concentrated in vacuo to give a viscous oil. The crude product was purified by flash column chromatography (silica gel, methylene chloride) and the resulting product was then dried in vacuo (40° C., <1 mmHg) to afford 0.75 g (60%) of a slightly impure product as a white solid: mp 73.5-75.0° C.; 1H NMR (CDCl3) δ 7.80-7.72 (m, 2H), 7.63-7.15 (m, 5H), 6.94-6.79 (m, 1H), 4.91-4.78 (m, 1H), 3.92 (s, 3H), 2.09-1.50 (m, 8H) also some impurity in the aromatic region; 13C NMR (CDCl3) δ 195.7, 153.9, 147.5, 138.3, 131.8, 129.7, 128.1, 125.1, 120.3, 115.5, 110.3, 80.5, 56.1, 32.7, 24.1; HPLC (Waters Nova-Pak/C18 column, 3.9×150mrn, 4 micron, 1 mL/min, 60/40, CH3CN/0.1% H3PO4(aq)) 6.2, min 99%.

Workup

  1. temperatureTo an ice bath cooled
  2. customA white gum precipitated from the mixture and dry THF (6 mL)
  3. additionwas added
  4. stirringwas stirred for 4 hours
  5. customThe reaction was then quenched at 0° C. with a saturated aqueous solution of ammonium chloride (8 mL)
  6. temperatureto warm to room temperature
  7. additionwas diluted with ethyl acetate (10 mL)
  8. customThe organic layer was separated
  9. washsequentially washed with 1 N citric acid (2×10 mL), saturated NaHCO3(aq) (2×10 mL), and brine (2×10 mL)
  10. dry with materialThe organic layer was then dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give a viscous oil
  14. customThe crude product was purified by flash column chromatography (silica gel, methylene chloride)
  15. customthe resulting product was then dried in vacuo (40° C., <1 mmHg)
  16. customto afford 0.75 g (60%) of a slightly impure product as a white solid

Sources & evidence

ORD record
ord-496a703d8aba4da99a3df98f1fe49277
Source dataset
uspto-grants-1999_07
Patent number
US05929117

Reaction notes

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