Reaction #343726

Reaction equation

9

(S)-11-Hydroxyaporphine Hydrochloride

HCl

hexamethylphosphorous triamide

NaHCO3

HCl

MeMgBr

HCl

paraformaldehyde

→

white solid

Yield 46.0%

(S)-10-Formyl-11-hydroxyaporphine Hydrochloride

Yield 46.0%

Solvents

benzene

benzene

benzene

benzene

Conditions

Workup

1. 1
   OtherThis reaction was performed in a dry box under N2 (10% relative humidity)
2. 2
   workup.STIRRINGThe mixture was stirred for 15 min
3. 3
   workup.ADDITIONwas added
4. 4
   TemperatureThe mixture was heated
5. 5
   Temperatureunder reflux for 4 h
6. 6
   Temperaturecooled
7. 7
   workup.STIRRINGthe resulting mixture was stirred for 10 min
8. 8
   Extractionwas extracted with 100 mL of Et2O
9. 9
   DryingThe combined extracts were dried (Na2SO4) and volatiles
10. 10
    Otherwere removed under reduced pressure
11. 11
    Otherto produce a green oil which
12. 12
    WashThe salt was washed with two 5 mL portions of abs EtOH

Procedure

This reaction was performed in a dry box under N2 (10% relative humidity). A suspension of 0.228 g (0.908 mmol) of 9 in 10 mL of benzene was added in 0.5 mL portions over 20 min to a solution of 0.45 mL (1.36 mmol) of MeMgBr (3.0M in Et2O) in 10 mL of benzene. The mixture was stirred at room temperature for 30 min. A solution of 0.243 g (1.36 mmol) of hexamethylphosphorous triamide in 1 mL of benzene was added. The mixture was stirred for 15 min, then a suspension of 0.273 g (9.08 mmol) of paraformaldehyde in 2 mL of benzene was added. The mixture was heated under reflux for 4 h, cooled, and transferred to a 1 L beaker. Two hundred milliliters of 5% HCl was added and the resulting mixture was stirred for 10 min. The mixture was made basic with solid NaHCO3 and was extracted with 100 mL of Et2O, then with four 75 mL portions of CHCl3. The combined extracts were dried (Na2SO4) and volatiles were removed under reduced pressure to produce a green oil which was converted into its HCl salt with ethereal HCl. The salt was washed with two 5 mL portions of abs EtOH to give 0.130 g (46%) of a white solid, mp 255°-258° C. (decomp). Lit1 mp of (R) enantiomer 260°-262° C. (decomp).

Source