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Potassium Carbonate → 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

HRID 604684
ノート
印刷プレビュー

反応式

HRID 604684 の反応式
[F:1][C:2]([F:48])([F:47])[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][CH3:43])=[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](Cl)[N:21]=3)[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:49]1(B(O)O)[CH2:51][CH2:50]1.C([O-])([O-])=O.[K+].[K+]>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].C1COCC1>[F:1][C:2]([F:48])([F:47])[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][CH3:43])=[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:49]4[CH2:51][CH2:50]4)[N:21]=3)[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 57576282methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate2 回

生成物 1

HCID 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

試薬・触媒・溶媒 2

HCID 178454861HCID 178454861、化合物触媒HCID 8028Tetrahydrofuran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-chloropyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (EXAMPLE 59 100 mg, 0.144 mmol), cyclopropylboronic acid (62.0 mg, 0.721 mmol), 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (19.62 mg, 0.029 mmol), aqueous K2CO3 (1M, 1.010 mL, 1.010 mmol) and THF (1.002 mL) were stirred at 80° C. for 3.5 h then slowly cooled to ambient overnight. Volatiles were removed under reduced pressure. The resulting pot residue was worked up with brine, extracted with EtOAc, dried (Na2SO4), filtered and evaporated to a dark mixture. The mixture was purified by reverse-phase preparative 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 aqueous mixture was extracted with EtOAc, washed with aqueous NaHCO3, dried (Na2SO4), filtered and concentrated to afford the titled compound. LCMS calc.=698.22; found=699.30 (M+H)+.

後処理

  1. customwere stirred at 80° C. for 3.5 h
  2. temperaturethen slowly cooled to ambient overnight
  3. customVolatiles were removed under reduced pressure
  4. extractionextracted with EtOAc
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated to a dark mixture
  8. customThe mixture was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  9. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min)
  10. customevaporated in vacuo
  11. customto afford an aqueous mixture
  12. extractionThe aqueous mixture was extracted with EtOAc
  13. washwashed with aqueous NaHCO3
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated

出典と根拠

ORDレコード
ord-5f5bbf0cabe740419215159f4f25bf06
出典データセット
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07910592B2

反応ノート

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