Hydrochloric Acid → 3'-[2-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

HRID 604685ノート

反応式

HRID 604685 の反応式
[F:1][C:2]([F:50])([F:49])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([O:42]C)=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:45]4[CH2:47][CH2:46]4)[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[Li+].O1CCOCC1.Cl>O>[F:50][C:2]([F:1])([F:49])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([OH:42])=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:45]4[CH2:46][CH2:47]4)[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrateHCID 86627637Methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

生成物 1

HCID 249690113'-[2-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

Methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (70 mg, 0.100 mmol), lithium hydroxide monohydrate (21.02 mg, 0.501 mmol), 1,4-dioxane (1.670 mL) and water (1.670 mL) were stirred at room temperature. LCMS indicated about 8% conversion when reaction time was 1 h. LCMS trace of reaction aliquot at reaction time 18 h indicated completion of reaction. Reaction mixture was acidified by HCl (aq., 1N). Volatiles were removed under reduced pressure. The resulting pot residue was purified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min). Related fractions were pooled and evaporated in vacuo to afford an aqueous mixture. The resulting aqueous mixture was extracted with EtOAc, washed with water, dried (Na2SO4), filtered and concentrated to afford a light yellow solid as the titled compound. LCMS calc.=684.21; found=685.96 (M+1)+. 1H NMR (500 MHz, CDCl3, 2:1 mixture of atropisomers): δ 8.02-7.90 (m, 3H), 7.85 (s, 1H), 7.70 (s, 2H), 7.50-7.44 (m, 1H), 7.37-7.28 (m, 1.5H), 7.16-7.09 (m, 2.5H), 5.70 (d, J=7 Hz, 0.67H), 5.63 (d, J=7.5 Hz, 0.33), 5.02 (d, J=15-5 Hz, 0.5H), 4.72 (d, J=15.5 Hz, 0.5H), 4.59 (d, J=16 Hz, 0.5H), 4.46 (d, J=16 Hz, 0.5H), 4.44-4.36 (m, 0.67H), 4.14-4.22 (m, 0.33H), 3.92-3.84 (m, 3H), 2.71 (br s, 0.67H), 2.61 (br s, 0.33H), 2.39 (s, 2H), 2.35 (s, 1H), 2.51-1.40 (m, 2H), 1.15-1.10 (m, 2H), 0.74 (d, J=6.5 Hz, 2H), 0.65 (d, J=5.5 Hz, 1H).

後処理

  1. customabout 8% conversion when reaction time
  2. customLCMS trace of reaction aliquot
  3. customat reaction time 18 h
  4. customcompletion of reaction
  5. customReaction mixture
  6. customVolatiles were removed under reduced pressure
  7. customThe resulting pot residue was purified by a reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  8. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min)
  9. customevaporated in vacuo
  10. customto afford an aqueous mixture
  11. extractionThe resulting aqueous mixture was extracted with EtOAc
  12. washwashed with water
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated

出典と根拠

ORDレコード
ord-2baf1e03954b45ad95fe6901ff1bb042
出典データセット
uspto-grants-2011_03
特許番号
US07910592B2

反応ノート

読み込み中…