Hydrochloric Acid → 2-Cyclopropyl-6-hydroxypyrimidine-4-carboxylic acid

HRID 249651

반응식

HRID 249651 반응식
[Na].[C:2]([O:12]CC)(=[O:11])[CH2:3][C:4]([C:6]([O:8]CC)=O)=O.[OH-].[Na+].Cl.[CH:18]1([C:21](=[NH:23])[NH2:22])[CH2:20][CH2:19]1.Cl>CO.O>[CH:18]1([C:21]2[NH:23][C:6](=[O:8])[CH:4]=[C:3]([C:2]([OH:12])=[O:11])[N:22]=2)[CH2:20][CH2:19]1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2781916Cyclopropanecarboximidamide hydrochlorideHCID 57351814Diethyl 2-oxosuccinate,sodium salt

생성물 1

HCID 1355475272-Cyclopropyl-6-hydroxypyrimidine-4-carboxylic acid수율 46.6%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매2회

반응 조건

온도
30 °C

실험 절차

To a mixture of diethyl oxalacetate sodium salt (150 g, 714 mmol) in methanol (300 mL) and water (150 mL) warmed to 30° C. was added 50% aqueous sodium hydroxide (56 g, 700 mmol) in water (60 mL) over 30 minutes, over which time the temperature remained at 25-30° C. and the pH at 11-12. Then the stirred mixture was heated for an additional 30 min at 35° C. To this mixture was added cyclopropanecarboximidamide monohydrochloride (64 g, 530 mol) in portions over 15 minutes. The orange solution was heated to 50° C. over 30 minutes and held at that temperature for 3 h. The reaction mixture was cooled to 35° C., and concentrated hydrochloric acid (ca. 70 g, 0.7 mol) was added gradually (resulting in foaming) over 30 minutes at 30-40° C. until the pH was about 1.5-2.5. The mixture was concentrated with a rotary evaporator at 35-40° C. to remove alcohols, stirred for 3-4 h at 25° C. to complete crystallization of the product. After the mixture was cooled to 0° C. the solid was collected by filtration. The solid washed with water (2×60 mL), suction-dried, and then dried in a vacuum-oven at 60° C. to afford the title compound as a beige solid (ca. 60 g).

후처리

  1. customremained at 25-30° C.
  2. temperatureThen the stirred mixture was heated for an additional 30 min at 35° C
  3. temperatureThe orange solution was heated to 50° C. over 30 minutes
  4. temperatureThe reaction mixture was cooled to 35° C.
  5. custom(resulting in foaming) over 30 minutes at 30-40° C. until the pH was about 1.5-2.5
  6. concentrationThe mixture was concentrated with a rotary evaporator at 35-40° C.
  7. customto remove alcohols
  8. customcrystallization of the product
  9. temperatureAfter the mixture was cooled to 0° C. the solid
  10. filtrationwas collected by filtration
  11. washThe solid washed with water (2×60 mL)
  12. customsuction-dried
  13. customdried in a vacuum-oven at 60° C.

출처 및 근거

ORD 기록
ord-b4a48c91ee8a41a2a219c1a5dd170780
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863220B2

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