Reaction #43265

Reaction equation

4-(iodomethyl)tetrahydro-2H-pyran

n-butyllithium

1,1,1,3,3,3-hexamethyldisilazane

ethyl (10-methyl-5,5-dioxo-5,10-dihydrophenothiazin-2-yl)acetate

→

Ethyl 2-(10-methyl-5,5-dioxo-5,10-dihydrophenothiazin-2-yl)-3-(tetrahydropyran-4-yl)propionate

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture is stirred at −78° C. for 20 minutes
2. 2
   OtherThe cooling bath is removed
3. 3
   Temperatureto slowly warm to room temperature
4. 4
   workup.STIRRINGThe reaction mixture is stirred at room temperature overnight
5. 5
   workup.ADDITION10 ml of water are then added
6. 6
   Otherthe tetrahydrofuran is removed under reduced pressure
7. 7
   Extractionthe residue is extracted three times with in each case 100 ml of ethyl acetate
8. 8
   DryingThe combined organic phases are dried over MgSO4
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    OtherThe residue is purified on silica gel using the mobile phase n-heptane

Procedure

Under argon, 1.66 ml of 1,1,1,3,3,3-hexamethyldisilazane are dissolved in 20 ml of tetrahydrofuran. With ice cooling, 2.90 ml of n-butyllithium (2.5 M in n-hexane) are added dropwise, and the mixture is stirred at 0° C. for another 30 minutes. At −78° C., this solution is then added dropwise to a stirred solution of 2.0 g of ethyl (10-methyl-5,5-dioxo-5,10-dihydrophenothiazin-2-yl)acetate in 100 ml of tetrahydrofuran. The reaction mixture is stirred at −78° C. for 20 minutes, and 2.0 g of 4-(iodomethyl)tetrahydro-2H-pyran are then added dropwise. The cooling bath is removed and the mixture is allowed to slowly warm to room temperature. The reaction mixture is stirred at room temperature overnight. 10 ml of water are then added, the tetrahydrofuran is removed under reduced pressure and the residue is extracted three times with in each case 100 ml of ethyl acetate. The combined organic phases are dried over MgSO4 and then concentrated under reduced pressure. The residue is purified on silica gel using the mobile phase n-heptane:ethyl acetate (100%:0%)=>n-heptane:ethyl acetate (0%:100%). This gives 2.0 g of ethyl 2-(10-methyl-5,5-dioxo-5,10-dihydrophenothiazin-2-yl)-3-(tetrahydropyran-4-yl)propionate as a colorless solid.

Source