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

HRID 2093217노트

반응식

HRID 2093217 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])=[C:41]([CH3:49])[CH:40]=4)[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.Cl>CCOC(C)=O.O1CCOCC1>[F:52][C:2]([F:1])([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:27])([F:28])[F:29])[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])=[C:41]([CH3:49])[CH:40]=4)[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

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 57704852Methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6'-fluoro-4'-methoxy-3-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

생성물 1

HCID 250091592''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6'-fluoro-4'-methoxy-3-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic Acid

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 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)-6′-fluoro-4′-methoxy-3-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (55 mg, 0.074 mmol), lithium hydroxide monohydrate (31 mg, 0.74 mmol), water (1 mL) and 1,4-dioxane (2 mL) were stirred at room temperature overnight. LCMS trace of reaction aliquot indicated completion of reaction. Crude mixture was acidified by HCl (1N aq.). Volatiles were removed under reduced pressure. Pot residue was dissolved in a water/MeCN mixture and purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture. Corresponding fractions were pooled & evaporated in vacuo to afford a light yellow glass. This residue was dissolved in EtOAc and washed w/water (10 mL×2), separated, dried/Na2SO4, filtered and concentrated to afford the title compound. LCMS (ESI) calc.=729.16; found=730.15 (M+1)1. 1H NMR (CDCl3, 500 MHz, 1:1 mixture of atropisomers): δ 8.10 (t, J=7.8 Hz, 1H), 7.85 (d, J=5 Hz, 1H), 7.70 (s, 1.5H), 7.66 (d, J=8 Hz, 1H), 7.62 (s, 1.5H), 7.47-7.38 (m, 3H), 7.30-7.25 (m, 1H), 6.85 (dd, J=12.5, 3 Hz, 1H), 5.61 (d, J=8 Hz, 0.5H), 5.31 (d, J=8 Hz, 0.5H), 4.94 (d, J=4.5 Hz, 0.5H), 4.91 (d, J=4 Hz, 0.5H), 4.15 (d, J=16.5 Hz, 0.5H), 3.93 (d, J=16 Hz, 0.5H), 3.86 (s, 3H), 3.86-3.76 (m, 1H), 2.68 (s, 3H), 0.57 (d, J=6.5 Hz, 1.5H), 0.46 (d, J=6.5 Hz, 1.5H).

후처리

  1. customLCMS trace of reaction
  2. customcompletion of reaction
  3. customVolatiles were removed under reduced pressure
  4. dissolutionPot residue was dissolved in a water/MeCN mixture
  5. custompurified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  6. washeluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
  7. customevaporated in vacuo
  8. customto afford a light yellow glass
  9. washwashed w/water (10 mL×2)
  10. customseparated
  11. dry with materialdried/Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated

출처 및 근거

ORD 기록
ord-3c1c0e6a9ced4d2e8c8cc05da943de53
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08440702B2

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