4-Methylmorpholine → rac-{2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidin-5-yl}methanol

HRID 38769노트

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HRID 38769 반응식
[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]([C:19](O)=[O:20])=[CH:11][N:10]=1.CN1CCOCC1.ClC(OCC(C)C)=O>COCCOC>[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[NH:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[C:12]([CH2:19][OH:20])=[CH:11][N:10]=1

참가 물질

5

반응물 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 66720245rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid

생성물 1

HCID 66720204rac-{2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidin-5-yl}methanol수율 55.1%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

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온도
-10 °C

실험 절차

A mixture of rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid (2.0 g), 4-methyl morpholine (1.1 mL) and 1,2-dimethoxyethane (40 mL) was cooled to −10° C., isobutyl chloroformate (1.1 mL) was added thereto, and the mixture was stirred at the same temperature for 1 hour. The insoluble materials in the reaction mixture were filtered and washed with 1,2-dimethoxyethane. The filtrate was cooled to −60° C. and a solution of sodium borohydride (377 mg) in water (4.0 mL) was added thereto, followed by stirring as it is for 1 hour. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=10:90 to 20:80) to obtain rac-{2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino]-4-(trifluoromethyl)pyrimidin-5-yl}methanol (1.05 g) as a colorless oily substance.

후처리

  1. filtrationThe insoluble materials in the reaction mixture were filtered
  2. washwashed with 1,2-dimethoxyethane
  3. temperatureThe filtrate was cooled to −60° C.
  4. additiona solution of sodium borohydride (377 mg) in water (4.0 mL) was added
  5. stirringby stirring as it
  6. waitis for 1 hour
  7. additionTo the reaction mixture was added water
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe organic layer was washed with water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=10:90 to 20:80)

출처 및 근거

ORD 기록
ord-b597ceaf3b364db28b9e915f6e5f73be
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524727B2

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