Water → Benzyl 4-[1-(2-chloro-pyridin-3-yl)-ureido]-piperidine-1-carboxylate

HRID 1846421노트

반응식

HRID 1846421 반응식
ClS([N:5]=[C:6]=[O:7])(=O)=O.[Cl:8][C:9]1[C:14]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[CH2:18][CH2:17]2)=[CH:13][CH:12]=[CH:11][N:10]=1.O.[OH-].[Na+]>C1COCC1>[Cl:8][C:9]1[C:14]([N:15]([CH:16]2[CH2:17][CH2:18][N:19]([C:22]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[O:23])[CH2:20][CH2:21]2)[C:6]([NH2:5])=[O:7])=[CH:13][CH:12]=[CH:11][N:10]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 70918Chlorosulfonyl isocyanateHCID 46853853Benzyl 4-(2-chloro-pyridin-3-yl-amino)-piperidine-1-carboxylate

생성물 1

HCID 46853854Benzyl 4-[1-(2-chloro-pyridin-3-yl)-ureido]-piperidine-1-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-15 °C

실험 절차

530 mL (6.1 mol) chlorosulphonyl isocyanate were placed in 6 L of THF and cooled to −15° C. A solution of 1.25 kg (3.63 mol) benzyl 4-(2-chloro-pyridin-3-yl-amino)-piperidine-1-carboxylate in 7 L THF was then added dropwise to this mixture within one hour in such a way that the temperature of the reaction mixture did not exceed −7° C. The mixture was stirred for 90 minutes at approx. −8° C. and then 700 mL water was added dropwise within 30 minutes. The mixture was stirred for 30 minutes at approx. 10° C. and then slowly combined with 8.1 L sodium hydroxide solution (2 mol/L). The reaction mixture was then heated to 50° C. and the phases were separated. The organic phase was washed with 2 L water. Then 10 L solvent were distilled off from the organic phase, 15 L butyl acetate were added to the residue and another 8 L were distilled off again. The product was crystallised by slowly cooling to 0° C. The precipitate was suction filtered, washed with 2 L butyl acetate and dried at 40° C.

후처리

  1. customdid not exceed −7° C
  2. stirringThe mixture was stirred for 30 minutes at approx. 10° C.
  3. temperatureThe reaction mixture was then heated to 50° C.
  4. customthe phases were separated
  5. washThe organic phase was washed with 2 L water
  6. distillationThen 10 L solvent were distilled off from the organic phase, 15 L butyl acetate
  7. additionwere added to the residue
  8. distillationanother 8 L were distilled off again
  9. customThe product was crystallised
  10. temperatureby slowly cooling to 0° C
  11. filtrationfiltered
  12. washwashed with 2 L butyl acetate
  13. customdried at 40° C.

출처 및 근거

ORD 기록
ord-aae889df1f364cfbbe0f6905b7d586bf
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952014B2

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