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

HRID 38769ノート

反応式

HRID 38769 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
-10 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-b597ceaf3b364db28b9e915f6e5f73be
出典データセット
uspto-grants-2013_09
特許番号
US08524727B2

反応ノート

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