Potassium bisulfate → (trans)-N-[[2-(3-methoxyphenyl)cyclopropyl]methyl]butanamide

HRID 1419950Notes

Reaction equation

HRID 1419950 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@@H:9]2[CH2:11][C@H:10]2[CH:12]=O)[CH:6]=[CH:7][CH:8]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].CO[N:22](C)[C:23]([C@@H:25]1[CH2:27][C@H:26]1C1C=CC=C(OC)C=1)=[O:24].S([O-])(O)(=O)=O.[K+]>C1COCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@@H:9]2[CH2:11][C@H:10]2[CH2:12][NH:22][C:23](=[O:24])[CH2:25][CH2:26][CH3:27])[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 516920Potassium bisulfateHCID 21226445Aluminium lithium hydrideHCID 53772372(trans)-N-Methoxy-N-methyl-2-(3-methoxyphenyl)cyclopropanecarboxamideHCID 54374070(trans)-2-(3-Methoxyphenyl)cyclopropanecarboxaldehyde

Product 1

HCID 15860309(trans)-N-[[2-(3-methoxyphenyl)cyclopropyl]methyl]butanamideYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

(trans)-2-(3-Methoxyphenyl)cyclopropanecarboxaldehyde: To a rapidly stirred suspension of LiAlH4 (7.74 g, 204 mmol) in THF (800 mL) at -45° C. was added a solution of the (trans)-N-methoxy-N-methyl-2-(3-methoxyphenyl)cyclopropanecarboxamide (40 g, 171 mmol) in THF (100 mL) maintaining the temperature below -40° C. by dropwise addition. After addition the cooling bath was removed and the reaction was allowed to warm to 5° C., then immediately recooled to -45° C. Potassium hydrogen sulfate (40 g, 300 mmol) in H2O(120 mL) was cautiously added dropwise, the temperature maintained below -30° C. throughout. After addition the cooling bath was removed and the suspension was stirred at room temperature for 30 min. The mixture was filtered through celite and the filter cake was washed with ether. The combined filtrates were then washed with cold 1N HCl, 5% K2CO3, brine, and dried over MgSO4. Concentration by rotary evaporation yielded the title compound as a clear oil (29.9 g, 99%): 1H NMR (300 MHz, CDCl3) δ 1.49-1.58 (m, 1H), 1.65-1.73 (m, 1H), 2.10-2.19(m, 1H), 2.58-2.67 (m, 1H), 3.80 (s, 3H), 6.66-6.78 (m, 3H), 7.21 (t, J=6.6 Hz, 1H), 9.32 (d, J=2.0 Hz, 1H).

Workup

  1. temperaturemaintaining the temperature below -40° C.
  2. additionby dropwise addition
  3. additionAfter addition the cooling bath
  4. customwas removed
  5. customimmediately recooled to -45° C
  6. temperaturethe temperature maintained below -30° C. throughout
  7. additionAfter addition the cooling bath
  8. customwas removed
  9. filtrationThe mixture was filtered through celite
  10. washthe filter cake was washed with ether
  11. washThe combined filtrates were then washed with cold 1N HCl, 5% K2CO3, brine
  12. dry with materialdried over MgSO4
  13. concentrationConcentration
  14. customby rotary evaporation

Sources & evidence

ORD record
ord-38a2e0d45c72444cbb2f07eb8bf39211
Source dataset
uspto-grants-1999_03
Patent number
US05889031

Reaction notes

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