Chloromethyl Methyl Ether → HCID 122643080、化合物

HRID 2272337ノート

反応式

HRID 2272337 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-789ed713e0c44886b52c1aa3d4d9deb9
出典データセット
uspto-grants-2015_09
特許番号
US09119868B2

反応ノート

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