Hydrochloric Acid → tert-butyl (2-(1-methyl-1H-pyrazol-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)carbamate

HRID 512210

반응식

HRID 512210 반응식
[CH3:1][N:2]1[CH:6]=[C:5]([CH:7]([C:14]2[CH:15]=[N:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=2)[CH2:8]C(OCC)=O)[CH:4]=[N:3]1.C[Si](C)(C)O.[Na].Cl.CC[O:33][CH2:34]C.C[N:37]1C=C(C(C2C=NC(C(F)(F)F)=CC=2)CC(O)=O)C=N1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:74]([OH:78])([CH3:77])([CH3:76])[CH3:75]>O.C1COCC1>[CH3:1][N:2]1[CH:6]=[C:5]([CH:7]([C:14]2[CH:15]=[N:16][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:18][CH:19]=2)[CH2:8][NH:37][C:34](=[O:33])[O:78][C:74]([CH3:77])([CH3:76])[CH3:75])[CH:4]=[N:3]1

참가 물질

11

반응물 8

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6386tert-ButanolHCID 66110Trimethylsilanol2회HCID 199401P,P-Diphenylphosphinic azideHCID 5360545Sodium2회HCID 86716242Ethyl 3-(1-methyl-1H-pyrazol-4-yl)-3-(6-(trifluoromethyl)pyridin-3-yl)propanoateHCID 867162433-(1-methyl-1H-pyrazol-4-yl)-3-(6-(trifluoromethyl)pyridin-3-yl)propanoic acid

생성물 1

HCID 86716241tert-butyl (2-(1-methyl-1H-pyrazol-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)carbamate수율 7%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

실험 절차

Ethyl 3-(1-methyl-1H-pyrazol-4-yl)-3-(6-(trifluoromethyl)pyridin-3-yl)propanoate (1.15 g, 3.51 mmol) was mixed with trimethylsilanol, sodium salt solution in THF (30 ml, 30.0 mmol, 1 molar) and stirred for 24 hours at room temperature. Trimethylsilanol, sodium salt solution in THF (30 ml, 30.0 mmol, 1 molar) added and mixture stiffed overnight at room temperature, LCMS shows incomplete comversion and reaction heated at reflux for 3 hours. The mixture was cooled on an ice bath and HCl in Et2O (48.0 g, 40 ml, 80 mmol, 2 molar) was added and after 10 min the mixture was concentrated in vacuo. The crude reaction mixture was then suspended dry THF (150 mL) and the solid filtred off. The liquid phase was concentrated in vacuo and used for next step without purification. 3-(1-methyl-1H-pyrazol-4-yl)-3-(6-(trifluoromethyl)pyridin-3-yl)propanoic acid (0.531 g, 1.774 mmol) dissolved in tert-butanol (10 ml. TEA (0.395 g, 0.544 ml, 3.90 mmol) and diphenylphosphoryl azide (0.59 g, 0.46 ml, 2.1 mmol) were added. Heated at 80° C. for 29 hours. The reaction was poured into H2O (50 mL) and extracted with EA (3×50 mL), the combined org. phases washed with brine, dried over MgSO4, concentrated in vacuo and purified by flash chromatography to yield 49 mg (7%) tert-butyl (2-(1-methyl-1H-pyrazol-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)carbamate.

후처리

  1. custommixture stiffed overnight
  2. customat room temperature
  3. customcomversion and reaction
  4. temperatureheated
  5. temperatureat reflux for 3 hours
  6. temperatureThe mixture was cooled on an ice bath
  7. concentrationwas concentrated in vacuo
  8. customThe crude reaction mixture
  9. concentrationThe liquid phase was concentrated in vacuo
  10. customused for next step without purification
  11. temperatureHeated at 80° C. for 29 hours
  12. extractionextracted with EA (3×50 mL)
  13. washphases washed with brine
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated in vacuo
  16. custompurified by flash chromatography

출처 및 근거

ORD 기록
ord-5c022fbd21bb42ebb70e3715b292eac0
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102591B2

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