Reaktion #45047

Reaktionsgleichung

Methyl 2-iodobenzoate

1-(3-Methylisoxazol-5-yl)methanamine

potassium phosphate

S-Phos

→

methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate

Ausbeute 45.6%

Lösungsmittel

water

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITat 90° C. for 6 h
2. 2
   Temperaturto cool
3. 3
   Extraktionextracted with ethyl acetate (3×60 ml)
4. 4
   WaschenThe combined extracts were washed with brine
5. 5
   Trocknendried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated
8. 8
   SonstigeThe residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which
9. 9
   Filtrationwas filtered off
10. 10
    SonstigeThe filtrate was evaporated
11. 11
    Sonstigetriturated again with methanol
12. 12
    Sonstigea second precipitate was removed by filtration
13. 13
    SonstigeThe filtrate was evaporated
14. 14
    Sonstigepurified by silica column chromatography
15. 15
    Wascheneluting with DCM
16. 16
    SonstigeThe product fractions were evaporated

Vorschrift

1-(3-Methylisoxazol-5-yl)methanamine (155 mg, 1.37 mmol, 1.2 eq), potassium phosphate (341 mg, 1.60 mmol, 1.4 eq), S-Phos (95 mg, 0.230 mmol, 0.2 eq) and Pd2dba3 (13 mg, 0.06 mmol, 0.05 eq) were stirred in toluene (5 ml) under nitrogen. Methyl 2-iodobenzoate (300 mg, 1.14 mmol, 1 eq) was added and the mixture was stirred at room temperature for 3 days, then at 90° C. for 6 h. The reaction mixture was allowed to cool, poured into water (100 ml) and extracted with ethyl acetate (3×60 ml). The combined extracts were washed with brine, dried over MgSO4, filtered and evaporated. The residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which was filtered off. The filtrate was evaporated and triturated again with methanol and a second precipitate was removed by filtration. The filtrate was evaporated, then purified by silica column chromatography, eluting with DCM. The product fractions were evaporated to afford methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate as a yellow oily gum (128 mg, 45% yield); 1H NMR (399.902 MHz, CDCl3) δ 2.25 (s, 3H), 3.88 (s, 3H), 4.53 (d, 2H), 5.99 (s, 1H), 6.62-6.70 (m, 2H), 7.32-7.38 (m, 1H), 7.92-7.96 (m, 1H), 8.19 (t, 1H). MS: m/z 247 (MH+)

Quelle