تفاعل #67625

معادلة التفاعل

Phosphorous oxychloride

5-Methoxy-2-nitrobenzoic acid

2-amino-5-chloropyridine

pyridine

→

2-nitro-N-(5-chloro-pyridin-2-yl)-5-methoxy-benzamide

المردود 88.2%

المذيبات

acetonitrile

water

ظروف التفاعل

المعالجة

1. 1
   أخرىwas adjusted to 22° C.
2. 2
   workup.ADDITIONwas added
3. 3
   غسيلThe pump and lines were rinsed forward with acetonitrile (22.5 kg, 0.9 parts)
4. 4
   أخرىwere adjusted to a temperature of 19-22° C
5. 5
   غسيلThe metering pump and lines were rinsed forward with acetonitrile (12.5 kg, 0.5 parts)
6. 6
   أخرىat 25° C.
7. 7
   أخرى(22-28° C.)
8. 8
   workup.ADDITIONafter the addition of about ⅓ of the POCl3
9. 9
   workup.ADDITIONAt the end of the addition, it
10. 10
    workup.ADDITIONAfter complete addition
11. 11
    أخرىreaction completion
12. 12
    درجة الحرارةThe solution was cooled to 15° C. (12-18° C.)
13. 13
    workup.ADDITIONwas charged slowly
14. 14
    أخرىreaction temperature of between 12 and 30° C
15. 15
    أخرىwas then adjusted to 22° C.
16. 16
    أخرى(19-25° C.)
17. 17
    workup.STIRRINGagitated for ca. 5 hrs
18. 18
    ترشيحthe contents of the reactor were filtered onto a pressure nutsche
19. 19
    أخرىfitted with a filter cloth
20. 20
    غسيلThe reactor, pump, and lines were washed forward onto the pressure nutsche with two portions of drinking water (62.5 kg, 2.5 parts each)
21. 21
    تجفيفThe product (41.8 kg) was dried under vacuum with a maximum temperature of water bath
22. 22
    درجة الحرارة(to heat dryer jacket) of 50° C
23. 23
    workup.WAITAfter ca. 12 hrs

الإجراء التجريبي

5-Methoxy-2-nitrobenzoic acid (A) (25.0 kg, 1.0 eq.), 2-amino-5-chloropyridine (B) (16.3 kg, 1.0 eq.), and acetonitrile (87.5 kg, 3.5 parts) were charged to a 380 L GLMS reactor. The reaction mixture was adjusted to 22° C. (19-25° C.) and anhydrous pyridine (30.0 kg, 3.0 eq.) was added. The pump and lines were rinsed forward with acetonitrile (22.5 kg, 0.9 parts), and the reactor contents were adjusted to a temperature of 19-22° C. Phosphorous oxychloride (23.3 kg, 1.20 eq.) was charged to the contents of the reactor via a metering pump, while maintaining a temperature of 25° C. (22-28° C.). The metering pump and lines were rinsed forward with acetonitrile (12.5 kg, 0.5 parts), while keeping the temperature at 25° C. (22-28° C.). The reaction mixture normally turned from a slurry to a clear solution after the addition of about ⅓ of the POCl3. At the end of the addition, it became turbid. After complete addition, the reaction mixture was agitated at 25° C. (22-28° C.) for ca. 1 hr, at which time HPLC analysis confirmed reaction completion. The solution was cooled to 15° C. (12-18° C.) and drinking water (156.3 kg, 6.25 parts) was charged slowly while keeping reaction temperature of between 12 and 30° C. The reaction mixture was then adjusted to 22° C. (19-25° C.) and agitated for ca. 5 hrs until exotherm ceased. Formation of a slurry was visually confirmed and the contents of the reactor were filtered onto a pressure nutsche fitted with a filter cloth. The reactor, pump, and lines were washed forward onto the pressure nutsche with two portions of drinking water (62.5 kg, 2.5 parts each). The filtrate had a pH value of 7. The product (41.8 kg) was dried under vacuum with a maximum temperature of water bath (to heat dryer jacket) of 50° C. After ca. 12 hrs, in-process LOD analysis indicated a solvent content of 0.72%. The dry product (C) was discharged (34.4 kg) with 88.2% yield and 99.1% purity by HPLC.

المصدر