Chloromethyl Methyl Ether → HCID 122643080、化合物

HRID 1424839ノート

反応式

HRID 1424839 の反応式
[Li+].[BH4-].[Br:3][C:4]1[C:13]([Cl:14])=[CH:12][C:11]([N:15]([C:20]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:23]3[C:24]([C:34](=[O:37])[NH:35][CH3:36])=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[O:26][C:22]=3[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])=[CH:10][C:5]=1[C:6](OC)=[O:7].CCN(C(C)C)C(C)C.[CH2:52](Cl)[O:53][CH3:54].C([O-])(O)=O.[Na+]>O1CCCC1.CO>[Br:3][C:4]1[C:5]([CH2:6][O:7][CH2:52][O:53][CH3:54])=[CH:10][C:11]([N:15]([C:20]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:23]3[C:24]([C:34]([NH:35][CH3:36])=[O:37])=[C:25]([C:27]4[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=4)[O:26][C:22]=3[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:13]=1[Cl:14]

参加物

8

反応物 5

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 122643076methyl 2-bromo-3-chloro-5-{N-[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl]methanesulfonamido}benzoate

生成物 1

HCID 122643080HCID 122643080、化合物収率 85.4%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

LiBH4 (2.85 ml, 5.71 mmol) solution (2M in THF) was added dropwise to a 0° C. solution of methyl 2-bromo-3-chloro-5-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)benzoate (1.24 g, 1.90 mmol) in Tetrahydrofuran (THF) (13.5 ml) and Methanol (1.3 ml). The reaction mixture was stirred at 0° C. for 1 h and quenched with 1M NaOH. The reaction mixture was diluted with EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated. The crude alcohol was taken up in THF (14 mL). DIEA (1.0 ml, 5.71 mmol) and MOM-Cl (0.36 ml, 4.76 mmol) were added and the reaction mixture was stirred at 50° C. overnight. Sat'd NaHCO3 was added and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-50% EtOAc/hexanes) to obtain the title compound (1.08 g, 85%) as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.86-7.93 (m, 2H), 7.61 (s, 1H), 7.50 (d, 1H), 7.49 (s, 1H), 7.42 (d, J=2.83 Hz, 1H), 7.18-7.25 (m, 2H), 5.80 (br. s., 1H), 4.73 (s, 2H), 4.62 (s, 2H), 3.38 (s, 3H), 3.27 (s, 3H), 3.01 (d, J=4.98 Hz, 3H), 2.05-2.14 (m, 1H), 0.75-1.11 (m, 3H), 0.58 (br. s., 1H).

後処理

  1. customquenched with 1M NaOH
  2. additionThe reaction mixture was diluted with EtOAc and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. stirringthe reaction mixture was stirred at 50° C. overnight
  8. extractionthe mixture was extracted with EtOAc
  9. washThe organic layer was washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated
  13. custompurified by silica gel chromatography (0-50% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-f42e9a99719f41e48d87e7954b608aba
出典データセット
uspto-grants-2015_01
特許番号
US08927593B2

反応ノート

読み込み中…