HCID 11512623、化合物 → HCID 11635729、化合物

HRID 1028589ノート

反応式

HRID 1028589 の反応式
[F:1][C:2]([F:39])([F:38])[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[S:31][CH:32]=[C:33]([CH:35]=[O:36])[N:34]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:40][Mg+].[Br-]>CCOCC>[F:39][C:2]([F:1])([F:38])[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:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[S:31][CH:32]=[C:33]([CH:35]([OH:36])[CH3:40])[N:34]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

参加物

4

反応物 2

HCID 11512623HCID 11512623、化合物HCID 178418689HCID 178418689、化合物2 回

生成物 1

HCID 11635729HCID 11635729、化合物

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒2 回

実験手順

To a −40° C. solution of 2-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl]-1,3-thiazole-4-carbaldehyde (Example 133) (43.9 mg, 0.075 mmol) in Et2O (7.5 mL) was added MeMgBr (30 μL of a 3M solution in Et2O, 0.10 mmol). The reaction was monitored closely by TLC and additional MeMgBr was added dropwise until nearly all starting aldehyde was consumed. At this point, the reaction was quenched by pouring it into saturated NH4Cl (15 mL). The mixture was extracted with EtOAc (50 mL) and the organic layer was washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (5 to 50% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[4-(1-hydroxyethyl)-1,3-thiazol-2-yl]-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.17 (40% EtOAc/hexanes). LCMS=599.1 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.70-7.86 (m, 6H), 7.31-7.32 (m, 1H), 5.53-5.55 (m, 1H), 5.35-5.41 (m, 1H), 5.06 (m, 1H), 4.57-4.62 (m, 1H), 3.88 (m, 1H), 1.61-1.63 (m, 3H), 0.69 (d, J=6.7 Hz, 3H).

後処理

  1. customwas consumed
  2. customAt this point, the reaction was quenched
  3. additionby pouring it into saturated NH4Cl (15 mL)
  4. extractionThe mixture was extracted with EtOAc (50 mL)
  5. washthe organic layer was washed with water and brine (15 mL each)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue by flash chromatography on silica gel (5 to 50% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-d1a62720a1214ec0af965953e73d409a
出典データセット
uspto-grants-2014_05
特許番号
US08735435B2

反応ノート

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