Reaction #40468

Reaction equation

4-benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester

Intermediate 17

4-benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester

tributyltin hydride

AIBN

→

4-benzyl-6,6-dimethyl-morpholine-3-carboxylic acid benzyl ester

Yield 85.0%

Solvents

toluene

toluene

Conditions

Workup

1. 1
   Temperatureto cool down
2. 2
   Concentrationwas concentrated to dryness
3. 3
   OtherThe residue was partitioned into 15% 1M HCl in acetonitrile and hexane
4. 4
   ExtractionThe separated hexane phase was extracted two times with the acetonitrile solution
5. 5
   WashThe combined acetonitrile solutions were washed with hexane two times
6. 6
   Concentrationconcentrated
7. 7
   OtherThe residue was partitioned into ether and 1M K2CO3
8. 8
   WashThe separated ether phase was washed successively with 0.4M Na2S2O3 and brine
9. 9
   Dryingdried over MgSO4
10. 10
    Concentrationconcentrated
11. 11
    OtherThe residue was purified on silica (7.5% EtOAc/hexane)

Procedure

To a solution of 4-benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester (Intermediate 17, 1.23 g) and tributyltin hydride (1.8 ml, 2.5 eq.) in 11 ml of toluene under gentle reflux was added over 1.5 hr a solution of AIBN in toluene (25 mg/1 ml). The mixture was allowed to cool down and was concentrated to dryness. The residue was partitioned into 15% 1M HCl in acetonitrile and hexane. The separated hexane phase was extracted two times with the acetonitrile solution. The combined acetonitrile solutions were washed with hexane two times and concentrated. The residue was partitioned into ether and 1M K2CO3. The separated ether phase was washed successively with 0.4M Na2S2O3 and brine, dried over MgSO4 and concentrated. The residue was purified on silica (7.5% EtOAc/hexane) to give 760 mg (oil, 85% yield) of compound 4-benzyl-6,6-dimethyl-morpholine-3-carboxylic acid benzyl ester.

Source