Water → rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylate

HRID 38774

반응식

HRID 38774 반응식
[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[OH:8].[H-].[Na+].Cl[C:12]1[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[C:15]([C:22]([O:24][CH3:25])=[O:23])=[CH:14][N:13]=1.O>O1CCCC1.[Cl-].[Na+].O>[CH:4]12[CH2:7][CH:1]([CH2:2][CH2:3]1)[CH2:6][CH:25]2[O:24][C:22]([C:15]1[C:16]([C:18]([F:21])([F:20])[F:19])=[N:17][C:12]([O:8][C@@H:2]2[CH2:3][C@@H:4]3[CH2:7][C@H:1]2[CH2:6][CH2:5]3)=[N:13][CH:14]=1)=[O:23]

참가 물질

7

반응물 4

HCID 962WaterHCID 24758Sodium hydrideHCID 790282-NorbornanolHCID 3696469Methyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate

생성물 1

HCID 66720285rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylate수율 44.3%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 57417360Sodium chloride; water용매

실험 절차

To a solution of rac-(1R,2R,4S)-bicyclo[2.2.1]heptan-2-ol (1.12 g) in tetrahydrofuran (10 mL) was added 60% sodium hydride (400 mg) under ice-cooling, and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was further stirred at an external temperature of 60° C. for 30 minutes, and then ice-cooled, and a mixture of methyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate (481 mg) and tetrahydrofuran (2 mL) was added thereto, followed by stirring at room temperature for 3 hours. To the reaction mixture were added water and saturated brine, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=100:0 to 97:3) to obtain a mixture (351 mg) of rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylate and rac-(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl2-[(1S,2S,4R)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylate as a colorless oily substance.

후처리

  1. temperaturecooling
  2. stirringThe reaction mixture was further stirred at an external temperature of 60° C. for 30 minutes
  3. temperatureice-cooled
  4. additionwas added
  5. stirringby stirring at room temperature for 3 hours
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe obtained organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=100:0 to 97:3)

출처 및 근거

ORD 기록
ord-3270fd3fb74749f0a5c99e80ffb37035
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524727B2

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