Hydrochloric Acid → (1R,2R,4S)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl) 4-hydroxy-cyclopentanecarboxylic acid tert-butyl ester

HRID 407598

반응식

HRID 407598 반응식
[C:1]([O:5][C:6]([CH:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[C:10](=[O:15])[O:11]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+].Cl.Cl.[CH2:20]([O:22][C:23]([C@@:25]1([NH2:30])[CH2:27][C@H:26]1[CH:28]=[CH2:29])=[O:24])[CH3:21].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCOCC1.O>[C:1]([O:5][C:6]([C@@H:8]1[CH2:13][C@@H:12]([OH:11])[CH2:14][C@H:9]1[C:10](=[O:15])[NH:30][C@:25]1([C:23]([O:22][CH2:20][CH3:21])=[O:24])[CH2:27][C@H:26]1[CH:28]=[CH2:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 591654183-Oxo-2-oxa-bicyclo[2.2.1]heptane-5-carboxylic acid tert-butyl esterHCID 66670028Cyclopropanecarboxylic acid, 1-amino-2-ethenyl-, ethyl ester, hydrochloride (1:1), (1R,2S)-

생성물 1

HCID 59165438(1R,2R,4S)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl) 4-hydroxy-cyclopentanecarboxylic acid tert-butyl ester수율 89%

시약·촉매·용매 1

HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
0 °C

실험 절차

Compound 146 (56 mg, 0.264 mmol) was dissolved in dioxane/water 1:1 (5 mL) and the mixture was cooled to 0° C. 1 M lithium hydroxide (0.52 mL, 0.520 mmol) was added and the mixture was stirred at 0° C. for 45 minutes, after which the mixture was neutralized with 1M hydrochloric acid and evaporated and coevaporated with toluene. The crystalline residue was dissolved in DMF (5 mL) and (1R,2S)-1-amino-2-vinyl-cyclopropane carboxylic acid ethyl ester hydrochloride (60 mg, 0.313 mmol) and diisopropylethylamine (DIEA) (138 μL, 0.792 mmol) were added and the solution was cooled to 0° C. HATU (120 mg, 0.316 mmol) was added and the mixture was stirred for 0.5 h at 0° C. and for an additional 2 h at room temperature. The mixture was then evaporated and extracted with EtOAc, washed with brine, dried, filtered and concentrated. Purification by flash column chromatography (toluene/EtOAc 1:1) provided the title compound (86 mg, 89%) as a colourless oil. The afforded oil was crystallised from ethyl acetate-hexane.

후처리

  1. customevaporated
  2. dissolutionThe crystalline residue was dissolved in DMF (5 mL)
  3. temperaturethe solution was cooled to 0° C
  4. stirringthe mixture was stirred for 0.5 h at 0° C. and for an additional 2 h at room temperature
  5. customThe mixture was then evaporated
  6. extractionextracted with EtOAc
  7. washwashed with brine
  8. customdried
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by flash column chromatography (toluene/EtOAc 1:1)

출처 및 근거

ORD 기록
ord-eb493a2bed1a43abb6843b914a7f9c94
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754106B2

연결된 노트

불러오는 중…