Reaktion #326559

Reaktionsgleichung

2-chloro-4-methylpyrimidine

Methyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorobenzoate

lithium bis(trimethylsilyl)amide

→

N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide

Ausbeute 76.4%

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was then stirred for 1 hr
2. 2
   SonstigeThe reaction was quenched with 4.5M HCl (3.92 L, 8 vols)
3. 3
   SonstigeThe aqueous layer (bottom layer) was removed
4. 4
   EinengenThe organic layer was concentrated under reduced pressure to ˜2 L
5. 5
   workup.ADDITIONIPAC (isopropyl acetate) (2.45 L) was added to the reaction mixture which
6. 6
   Einengenwas then concentrated to ˜2 L
7. 7
   workup.ADDITIONIPAC (0.5 L) and MTBE (2.45 L) was added
8. 8
   workup.STIRRINGstirred overnight under N2
9. 9
   FiltrationThe solids were filtered
10. 10
    workup.ADDITIONThe solids and mother filtrate added back together
11. 11
    workup.STIRRINGstirred for several hours
12. 12
    FiltrationThe solids were filtered
13. 13
    Waschenwashed with MTBE (˜5 vol)
14. 14
    SonstigeThe solids were dried in vacuum oven at 30° C. over weekend

Vorschrift

Methyl 3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorobenzoate (490 g, 1 equiv.), prepared generally in accordance with Step A, above, was dissolved in THF (2.45 L, 5 vols) and stirred and cooled to 0-3° C. 1M lithium bis(trimethylsilyl)amide in THF (5.25 L, 3.7 equiv.) solution was charged to the reaction mixture followed addition of 2-chloro-4-methylpyrimidine (238 g, 1.3 equiv.) in THF (2.45 L, 5 vols). The reaction was then stirred for 1 hr. The reaction was quenched with 4.5M HCl (3.92 L, 8 vols). The aqueous layer (bottom layer) was removed and discarded. The organic layer was concentrated under reduced pressure to ˜2 L. IPAC (isopropyl acetate) (2.45 L) was added to the reaction mixture which was then concentrated to ˜2 L. IPAC (0.5 L) and MTBE (2.45 L) was added and stirred overnight under N2. The solids were filtered. The solids and mother filtrate added back together and stirred for several hours. The solids were filtered and washed with MTBE (˜5 vol). The solids were placed in vacuum oven at 50° C. overnight. The solids were dried in vacuum oven at 30° C. over weekend to obtain N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (479 g, 72%).

Quelle