Hydrochloric Acid → HCID 11631837, compound

HRID 1454051Notes

Reaction equation

HRID 1454051 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]([C:16]#[N:17])=[CH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8][CH:7]=1.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Mg]Br.[CH3:29]I.Cl>C1COCC1>[CH3:1][O:2][C:3](=[O:18])[C:4]([C:16]#[N:17])([CH3:29])[CH:5]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[O:20][CH3:19])[C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 708094Methyl 2-cyano-3-(naphthalen-1-yl)prop-2-enoateHCID 178489560HCID 178489560, compound

Product 1

HCID 11631837HCID 11631837, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a 5-liter, 4-neck flask equipped with a mechanical stirrer, a condenser fitted with nitrogen inlet, a cooling bath and thermal couple were added 882 g anhydrous THF and 250 g (1.05 mol) 2-cyano-3-naphthalen-1-yl-acrylic acid methyl ester 1. The mixture was cooled to 5° C. and 1098 g (1.09 mol) of a 1 M THF solution of 2-methoxyphenylmagnesium bromide 2 was slowly charged into the reaction mixture through an addition funnel while maintaining the temperature at 0-10° C. The mixture was stirred for an additional 30 min. Methyl iodide (598 g, 4.21 mol) then was added in one portion. The mixture was stirred at 40° C. for 28 hours and then cooled to 25° C. The mixture was treated with 943 g of 0.5 N HCl and the lower aqueous phase was separated and retained. The organic layer was concentrated by distillation until 871 g distillate was collected. The organic concentrate then was cooled to 35° C. and the aqueous layer was combined with the organic. To the mixture then was added 506 g methanol. The mixture was cooled to 0° C. and the product was filtered. The wet cake was washed with a mixture of 333 g of methanol and 666 g of water. The product 3 was dried in an oven at 55° C. under vacuum. Yield: 306 g, 81%. The diastereomeric excess was typically 100%.

Workup

  1. customTo a 5-liter, 4-neck flask equipped with a mechanical stirrer, a condenser
  2. customfitted with nitrogen inlet, a cooling bath
  3. temperaturewhile maintaining the temperature at 0-10° C
  4. stirringThe mixture was stirred at 40° C. for 28 hours
  5. temperaturecooled to 25° C
  6. customthe lower aqueous phase was separated
  7. concentrationThe organic layer was concentrated by distillation until 871 g distillate
  8. customwas collected
  9. concentrationThe organic concentrate
  10. temperaturethen was cooled to 35° C.
  11. additionTo the mixture then was added 506 g methanol
  12. temperatureThe mixture was cooled to 0° C.
  13. filtrationthe product was filtered
  14. washThe wet cake was washed with a mixture of 333 g of methanol and 666 g of water
  15. dry with materialThe product 3 was dried in an oven at 55° C. under vacuum

Sources & evidence

ORD record
ord-c23924823ad54385846012b069a20996
Source dataset
uspto-grants-2009_01
Patent number
US07476752B2

Reaction notes

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