Sodium Hydroxide → Fasiglifam

HRID 1848781노트

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HRID 1848781 반응식
[OH:1][C:2]1[CH:15]=[CH:14][C:5]2[C@H:6]([CH2:9][C:10]([O:12]C)=[O:11])[CH2:7][O:8][C:4]=2[CH:3]=1.Cl[CH2:17][C:18]1[CH:19]=[C:20]([C:24]2[C:29]([CH3:30])=[CH:28][C:27]([O:31][CH2:32][CH2:33][CH2:34][S:35]([CH3:38])(=[O:37])=[O:36])=[CH:26][C:25]=2[CH3:39])[CH:21]=[CH:22][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>CN(C)C=O.O>[CH3:39][C:25]1[CH:26]=[C:27]([O:31][CH2:32][CH2:33][CH2:34][S:35]([CH3:38])(=[O:36])=[O:37])[CH:28]=[C:29]([CH3:30])[C:24]=1[C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([CH2:17][O:1][C:2]2[CH:15]=[CH:14][C:5]3[C@H:6]([CH2:9][C:10]([OH:12])=[O:11])[CH2:7][O:8][C:4]=3[CH:3]=2)[CH:19]=1

참가 물질

7

반응물 4

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 53393313(S)-Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateHCID 862228633'-(Chloromethyl)-2,6-dimethyl-4-[3-(methylsulfonyl)propoxy]biphenyl

생성물 1

HCID 24857286Fasiglifam수율 96.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

To a solution of methyl [(3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetate (10.0 g) and 3′-chloromethyl-2,6-dimethyl-4-[3-(methylsulfonyl)propoxy]biphenyl (17.6 g) in N,N-dimethylformamide (30.0 mL) was added tripotassium phosphate (16.8 g), and the mixture was stirred at 60° C. for 3 hr. 2.4M Aqueous sodium hydroxide solution (32.9 g) was added, and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was cooled, water (100 mL) was added, and the mixture was extracted with toluene (50 mL). To the aqueous layer was added toluene (50 mL), and the mixture was extracted. To the obtained aqueous layer were added acetone (10 mL) and concentrated hydrochloric acid (17.6 mL), and the mixture was stirred at 30° C. for 1 hr, at 50° C. for 30 min, and at 25° C. for 2 hr. The precipitated crystals were collected by filtration, and washed with a mixed solution (50 mL) of acetone.water (3:7) and then water (50 mL). The obtained crystals were dried at 60° C. under reduced pressure to give [(3S)-6-({2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid (24.3 g). 100% ee. (high performance liquid chromatography conditions)

후처리

  1. stirringthe mixture was stirred at 80° C. for 2 hr
  2. temperatureThe reaction mixture was cooled
  3. extractionthe mixture was extracted with toluene (50 mL)
  4. additionTo the aqueous layer was added toluene (50 mL)
  5. extractionthe mixture was extracted
  6. additionTo the obtained aqueous layer were added acetone (10 mL) and concentrated hydrochloric acid (17.6 mL)
  7. stirringthe mixture was stirred at 30° C. for 1 hr, at 50° C. for 30 min
  8. waitat 25° C. for 2 hr
  9. filtrationThe precipitated crystals were collected by filtration
  10. washwashed with a mixed solution (50 mL) of acetone
  11. customThe obtained crystals were dried at 60° C. under reduced pressure

출처 및 근거

ORD 기록
ord-4fc9d8617121456aba8bd5e2c99ea9ff
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952185B2

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