Formic Acid → Camptothecin

HRID 351985

반응식

HRID 351985 반응식
[CH3:1][CH2:2][C@@:3]1([OH:27])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:16](=[CH:17][C:4]1=2)[C:15]1[NH:18][C:19]2[C:25](=[CH:26][C:14]=1[CH2:13]3)[C:23](=O)[CH:22]=[CH:21][CH:20]=2)=[O:11].C(N(CC)CC)C.C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.C(O)=O>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CO.C(Cl)(Cl)Cl>[CH3:1][CH2:2][C@@:3]1([OH:27])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:16](=[CH:17][C:4]1=2)[C:15]1[N:18]=[C:19]2[C:25]([CH:23]=[CH:22][CH:21]=[CH:20]2)=[CH:26][C:14]=1[CH2:13]3)=[O:11]

참가 물질

9

반응물 4

HCID 284Formic AcidHCID 8471Triethylamine2회HCID 142176Phenyl triflimideHCID 178438219HCID 178438219, 화합물

생성물 1

HCID 24360Camptothecin수율 73.2%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 887Methanol용매2회HCID 6212Chloroform용매2회HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

To a solution of 9-hydroxycamptothecin (9-HC; 300 mg, 0.82 mmol) in N,N-dimethylformamide (15 ml), triethylamine (0.68 ml, 4.92 mmol. 6.0 eq.) and N-phenyl trifluoromethanesulfonimide (879 mg, 2.46 mmol, 3.0 eq.) were added, and the mixture was stirred at 60° C. for 0.5 hr under argon gas atmosphere. After confirmation of the disappearance of the starting material by thin layer chromatography (chloroform:methanol=20:1), this reaction solution was added with triethylamine (1.14 ml, 8.20 mmol. 10.0 eq.), dichlorobis(triphenylphosphine)palladium (58 mg, 0.08 mmol, 10 mol %), formic acid (189 mg, 4.10 mmol, 5.0 eq.) and heated at 60° C. for 3 hr. After the disappearance of 9-OTfC was confirmed by thin layer chromatography (chloroform:methanol=50:1), and the reaction mixture was cooled, followed by evaporation of the solvent under reduced pressure. The residue was added with chloroform (5 ml) and n-hexane (200 ml) and the resulting precipitate was taken by suction filtration to give camptothecin (CPT) (209 mg, yield 73%) as a yellow solid.

후처리

  1. temperatureheated at 60° C. for 3 hr
  2. temperaturethe reaction mixture was cooled
  3. customfollowed by evaporation of the solvent under reduced pressure
  4. additionThe residue was added with chloroform (5 ml) and n-hexane (200 ml)
  5. filtrationthe resulting precipitate was taken by suction filtration

출처 및 근거

ORD 기록
ord-8e1b706af2574fe18be9c493b5a14468
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06743918B2

연결된 노트

불러오는 중…