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Sodium hydride → methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 2093189
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HRID 2093189 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][C:10]=2[CH3:19])=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][C:21]=1[C@H:30]1[O:34][C:33](=[O:35])[NH:32][C@@H:31]1[CH3:36].[H-].[Na+].Br[CH2:40][C:41]1[CH:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[C:43]([C:51]([F:54])([F:53])[F:52])[CH:42]=1>C1COCC1>[F:48][C:47]([F:49])([F:50])[C:45]1[CH:46]=[C:41]([CH:42]=[C:43]([C:51]([F:54])([F:52])[F:53])[CH:44]=1)[CH2:40][N:32]1[C@H:31]([CH3:36])[C@@H:30]([C:21]2[CH:22]=[C:23]([C:26]([F:27])([F:28])[F:29])[CH:24]=[CH:25][C:20]=2[C:4]2[CH:5]=[C:6]([C:9]3[CH:14]=[CH:13][C:12]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][C:10]=3[CH3:19])[CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[O:34][C:33]1=[O:35]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 67065997methyl 4'-methoxy-2-methyl-2''-[(4R,5R)-4-methyl-2-oxo-1,3-oxazolidin-5-yl]-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

생성물 1

HCID 86630542methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

시약·촉매·용매

1
HCID 8028Tetrahydrofuran용매

실험 절차

The starting methyl 4′-methoxy-2-methyl-2″-[(4R,5R)-4-methyl-2-oxo-1,3-oxazolidin-5-yl]-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (40 mg, 0.080 mmol) was dissolved in anhydrous THF (1 mL) and cooled in an ice bath. Sodium hydride (60% w/w in mineral oil, 3.5 mg, 0.088 mmol) was added into the mixture. The reaction mixture was stirred cold (ice bath) for 10 min followed by addition of 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene (22 μL, 36.8 mg, 0.120 mmol). The resulting mixture was stirred cold for 20 min then the cold bath was removed. Aliquot at reaction time 2.5 hours indicated about 50% conversion. Reaction crude was cooled (ice bath) and quenched by NH4Cl (aq., sat.). The resulting bi-phasic mixture was worked up with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to afford an oil. This oil was purified by a preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm) eluted with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture. Related fractions were pooled and evaporated to afford methyl 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. Un-reacted starting material was also recovered. LCMS calc.=725.18; found=726.19 (M+1).

후처리

  1. temperaturecooled in an ice bath
  2. stirringThe resulting mixture was stirred cold for 20 min
  3. customthe cold bath was removed
  4. customAliquot at reaction time 2.5 hours
  5. customReaction crude
  6. temperaturewas cooled (ice bath)
  7. customquenched by NH4Cl (aq., sat.)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford an oil
  12. customThis oil was purified by a preparative reverse-phase HPLC (Kromasil 100-5C18, 100×21.1 mm)
  13. washeluted with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
  14. customevaporated

출처 및 근거

ORD 기록
ord-7442b154a06348a498acff90a228c030
출처 데이터셋
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08440702B2

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