Ammonium formate → Pregabalin

HRID 1034572노트

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HRID 1034572 반응식
C([O:3][C:4](=[O:15])[CH2:5][C@@H:6]([CH2:11][N+:12]([O-])=O)[CH2:7][CH:8]([CH3:10])[CH3:9])C.C([O-])=O.[NH4+]>CO.[Pd]>[CH3:10][CH:8]([CH2:7][C@H:6]([CH2:11][NH2:12])[CH2:5][C:4]([OH:15])=[O:3])[CH3:9]

참가 물질

5

반응물 2

HCID 2723923Ammonium formateHCID 29984078(S)-5-methyl-3-nitromethyl-hexanoic acid ethyl ester

생성물 1

HCID 5486971Pregabalin수율 81%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매

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온도
45 °C

실험 절차

(S)-5-Methyl-3-nitromethyl-hexanoic acid ethyl ester (VIII, R1=ethyl) (10.4 g) were dissolved in 160 mL of MeOH. 4 g of 10% Pd/C and 20 g of ammonium formate were added. After a few minutes an exothermic reaction was observed. After 30 minutes HPLC analysis indicated complete conversion. The catalyst was removed by filtration. The filtrate was concentrated under reduced pressure to a volume of about 20 mL. Water (20 mL) was added, then the solution was again concentrated unter reduced pressure to about 20 mL. Then 50 mL of 6N aqueous HCl were added and the mixture was refluxed for 6 hours. After complete conversion, the reaction mixture was concentrated under reduced pressure to about 20 mL. Water (20 mL) and 2-propanol (40 mL) were added and the reaction mixture was heated to 45° C. KOH was added until a pH of 7 was reached. The product started to crystallize. Within about 60 minutes the reaction mixture was cooled down to 10° C. Stirring was continued for 1 hour, then the product was isolated by filtration. The filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol. After drying, 5.9 g of substantially pure pregabalin (purity 98.0%) were obtained (yield: 81%).

후처리

  1. customAfter a few minutes an exothermic reaction
  2. customThe catalyst was removed by filtration
  3. concentrationThe filtrate was concentrated under reduced pressure to a volume of about 20 mL
  4. additionWater (20 mL) was added
  5. additionThen 50 mL of 6N aqueous HCl were added
  6. temperaturethe mixture was refluxed for 6 hours
  7. concentrationAfter complete conversion, the reaction mixture was concentrated under reduced pressure to about 20 mL
  8. additionWater (20 mL) and 2-propanol (40 mL) were added
  9. additionKOH was added until a pH of 7
  10. customto crystallize
  11. temperatureWithin about 60 minutes the reaction mixture was cooled down to 10° C
  12. waitwas continued for 1 hour
  13. customthe product was isolated by filtration
  14. washThe filter cake was washed with 90 mL of a 1:1 mixture of cold H2O/2-propanol
  15. customAfter drying

출처 및 근거

ORD 기록
ord-9f2445b77a97408085c538702f9c22c7
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546112B2

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