Reaktion #162593

Reaktionsgleichung

4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Na2CO3

3-(2,6-dichloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

3-(2,6-Dichloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

→

4-[2-chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-4-yl]-phenylamine

Ausbeute 16.0%

4-[4-chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-yl]-phenylamine

Ausbeute 15.0%

Lösungsmittel

toluene

ethanol

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto give a light yellow solution
2. 2
   SonstigeThe mixture was degassed
3. 3
   Sonstigeby bubbling nitrogen through the solution
4. 4
   Waschenwashed
5. 5
   TrocknenThe organic layer was dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   workup.ADDITIONThe crude product was added to a silica gel column
9. 9
   Waschenwas eluted with 20-80% ethyl acetate in hexanes
10. 10
    EinengenCollected fractions were concentrated

Vorschrift

In a 2-5 mL microwave vial was placed 3-(2,6-dichloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (9, 100 mg, 0.384 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (84 mg, 0.384 mmol) in toluene (1.500 mL) and ethanol (1 mL) to give a light yellow solution. Na2CO3 (2M solution in water) (0.769 mL, 1.538 mmol) was added. The mixture was degassed by bubbling nitrogen through the solution. Pd(PPh3)4 (22.21 mg, 0.019 mmol) was added. The reaction was heated under microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with ethyl acetate and washed with sat NaHCO3 (2×). The organic layer was dried over MgSO4, filtered and concentrated. The crude product was added to a silica gel column and was eluted with 20-80% ethyl acetate in hexanes. Collected fractions were concentrated to give 4-[2-chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-4-yl]-phenylamine (11, 19 mg, 16%) and 4-[4-chloro-6-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-pyrimidin-2-yl]-phenylamine (12, 18 mg, 15%).

Quelle