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 2093217ノート

反応式

HRID 2093217 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-3c1c0e6a9ced4d2e8c8cc05da943de53
出典データセット
uspto-grants-2013_05
特許番号
US08440702B2

反応ノート

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