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Water → 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic Acid

HRID 2093208
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HRID 2093208 반응식
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([O:47]C)=[O:46])=[CH:41][C:40]=4[F:49])[C:33]([F:38])=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[Li+].O>O1CCOCC1>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([OH:47])=[O:46])=[CH:41][C:40]=4[F:49])[C:33]([F:38])=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:50])[CH:4]=[C:3]([C:2]([F:52])([F:51])[F:1])[CH:8]=1
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참가 물질

5

반응물 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 57704789methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

생성물 1

HCID 250089942''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic Acid

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

methyl 2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6′-difluoro-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (50 mg, 0.067 mmol), lithium hydroxide monohydrate (28 mg, 0.67 mmol), water (1 mL) and 1,4-dioxane (2 mL) were stirred at room temperature for 2.5 hours. LCMS of aliquot indicated formation of the desired product and complete consumption of starting material. Crude mixture was acidified (1N HCl, aq.). Volatiles were removed under reduced pressure. Pot residue was dissolved in MeCN and purified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting w/MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v). Corresponding fractions were pooled and evaporated in vacuo to afford a mixture. The resulting mixture was extracted with EtOAc. The separated organic phases were back washed w/water, separated, dried/Na2SO4, filtered and evaporated to afford the title compound. LCMS (ESI) calc.=733.13; found=734.14 (M+1)+. 1H NMR (CDCl3, 500 MHz, 1:1 mixture of atropisomers): δ 7.95 (t, J=6 Hz, 1H), 7.89-7.83 (m, 2H), 7.73 (s, 0.5H), 7.71 (s, 1H), 7.68-7.64 (m, 2H), 7.62 (s, 0.5H) 7.58 (t, J=7 Hz, 0.5H), 7.53 (t, J=7.5 Hz, 0.5H), 7.42 (d, J=8 Hz, 0.5H), 7.39 (d, J=8 Hz, 0.5H), 7.31-7.23 (m, 1H), 6.89 (d, J=4 Hz, 0.5H), 6.87 (d, J=3.5Hz, 0.5H), 5.61 (d, J=8 Hz, 0.5H), 5.29 (d, J=8 Hz, 0.5H), 5.05 (d, J=16 Hz, 0.5H), 4.93 (d, J=16 Hz, 0.5H), 4.16 (d, J=16.5 Hz, 0.5H), 3.94 (d, J=16 Hz, 0.5H), 3.89 (s, 1.5H), 3.87 (s, 1.5H), 3.85-3.72 (m, 1H), 0.59 (d, J=7 Hz, 1.5H), 0.43 (d, J=6 Hz, 1.5H).

후처리

  1. customLCMS of aliquot indicated formation of the desired product and complete consumption of starting material
  2. customVolatiles were removed under reduced pressure
  3. dissolutionPot residue was dissolved in MeCN
  4. custompurified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  5. washeluting w/MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v)
  6. customevaporated in vacuo
  7. customto afford a mixture
  8. extractionThe resulting mixture was extracted with EtOAc
  9. washThe separated organic phases were back washed w/water
  10. customseparated
  11. dry with materialdried/Na2SO4
  12. filtrationfiltered
  13. customevaporated

출처 및 근거

ORD 기록
ord-d733a215bc5b445291f84d73efd82682
출처 데이터셋
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08440702B2

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