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-methoxyphenyl}acetate

HRID 604673ノート

反応式

HRID 604673 の反応式
[F:1][C:2]([F:42])([F:41])[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]([CH2:34][C:35]([O:37][CH3:38])=[O:36])[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[CH3:40])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:43]1(B(O)O)[CH2:45][CH2:44]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:42])([F:41])[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]([CH2:34][C:35]([O:37][CH3:38])=[O:36])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:43]4[CH2:45][CH2:44]4)[N:21]=3)[C@H:14]2[CH3:40])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 57576209methyl {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-methoxyphenyl}acetate

生成物 1

HCID 57576297methyl {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-methoxyphenyl}acetate

試薬・触媒・溶媒 2

HCID 178454861HCID 178454861、化合物触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

A flask was charged with 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-methoxyphenyl}acetate (42 mg, 0.0681 mmol), cyclopropyl boronic acid (58.5 mg, 0.681 mmol), 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (8.9 mg, 0.014 mmol), THF (1 mL), and 1M K2CO3 (1 mL, 1 mmol). The reaction was degassed with N2, and heated to 60° C. for 8 hours. The reaction was then cooled to room temperature, diluted with EtOAc (35 mL) and washed with water and brine (10 mL each). The organic layer was dried (Na2SO4), filtered, and concentrated. Purification of the residue by flash chromatography (0 to 70% EtOAc/hexanes) afforded 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-methoxyphenyl}acetate. LCMS=623-4 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 6.90-7.84 (m, 8H), 4.82-5.66 (m, 2H), 3.57-4.13 (m, 10H), 2.06 (m, 1H), 1.00-1.06 (m, 4H), 0.62 (bs, 3H).

後処理

  1. customThe reaction was degassed with N2
  2. temperatureThe reaction was then cooled to room temperature
  3. additiondiluted with EtOAc (35 mL)
  4. washwashed with water and brine (10 mL each)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography (0 to 70% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-969088c3a43b46738cb17434ae528601
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…