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 604685노트

반응식

HRID 604685 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 962Water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2baf1e03954b45ad95fe6901ff1bb042
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07910592B2

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