تفاعل #45047

معادلة التفاعل

Methyl 2-iodobenzoate

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

potassium phosphate

S-Phos

→

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

المردود 45.6%

المذيبات

water

toluene

ظروف التفاعل

المعالجة

1. 1
   workup.WAITat 90° C. for 6 h
2. 2
   درجة الحرارةto cool
3. 3
   استخلاصextracted with ethyl acetate (3×60 ml)
4. 4
   غسيلThe combined extracts were washed with brine
5. 5
   تجفيفdried over MgSO4
6. 6
   ترشيحfiltered
7. 7
   أخرىevaporated
8. 8
   أخرىThe residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which
9. 9
   ترشيحwas filtered off
10. 10
    أخرىThe filtrate was evaporated
11. 11
    أخرىtriturated again with methanol
12. 12
    أخرىa second precipitate was removed by filtration
13. 13
    أخرىThe filtrate was evaporated
14. 14
    أخرىpurified by silica column chromatography
15. 15
    غسيلeluting with DCM
16. 16
    أخرىThe product fractions were evaporated

الإجراء التجريبي

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+)

المصدر