반응 #328718

반응 방정식

cyanamide

methyl 4-amino-2-methoxybenzoate

nitric acid

→

5

수율 50.0%

methyl 4-{[amino(imino)methyl]amino}-2-methoxybenzoate nitrate

수율 50.0%

용매

methanol

methanol

반응 조건

후처리

1. 1
   온도The reaction mixture was heated
2. 2
   온도to reflux
3. 3
   기타a maximum jacket temperature of 75° C
4. 4
   온도The resulting mixture was heated
5. 5
   온도at reflux for 2 h
6. 6
   workup.ADDITIONwas added
7. 7
   workup.STIRRINGthe mixture was stirred
8. 8
   기타using a 75° C.
9. 9
   기타for 60 to 90 min
10. 10
    온도The mixture was cooled to 20 to 25° C. over at least 2 h
11. 11
    workup.STIRRINGstirred for an additional 2 h
12. 12
    여과The mixture was filtered
13. 13
    세척washed with methanol (180 L)
14. 14
    workup.STIRRINGwhile stirring for 1 h
15. 15
    세척The wet cake was washed a second time with methanol (180 L)
16. 16
    workup.STIRRINGwhile stirring for 1 h
17. 17
    기타The resulting wet cake was dried under vacuum at 25° C.

실험 절차

Into a reactor at room temperature was added methyl 4-amino-2-methoxybenzoate (4, 38 kg, 210 mol) and methanol (224 L). The mixture was stirred at 25 to 30° C. for 30 min. Aqueous cyanamide (50% w/w, 43 kg, 512 mol) was added over a minimum of 30min at 20 to 25° C. The reaction mixture was heated to reflux using a maximum jacket temperature of 75° C. Concentrated nitric acid (45 kg, 499 mol) was added over a minimum of 60 min. The resulting mixture was heated at reflux for 2 h. A suspension of seed crystals (16 g in 600 mL methanol) was added and the mixture was stirred using a 75° C. jacket temperature for 60 to 90 min. The mixture was cooled to 20 to 25° C. over at least 2 h and stirred for an additional 2 h. The mixture was filtered and washed with methanol (180 L) while stirring for 1 h. The wet cake was washed a second time with methanol (180 L) while stirring for 1 h. The resulting wet cake was dried under vacuum at 25° C. to provide 30.0 kg (50% yield) of 5. 1H NMR (300 MHz, DMSO-d6) δ 9.82 (s, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.57 (s, 4H), 6.97 (d, J=2.3 Hz, 1H), 6.84 (dd, J=2.3, 8.2 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H); MS (ESI) m/z 224.4 (M+, 100%).

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