Chloromethyl Methyl Ether → HCID 122643080, 화합물

HRID 1424839노트

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HRID 1424839 반응식
[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]

참가 물질

8

반응물 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

생성물 1

HCID 122643080HCID 122643080, 화합물수율 85.4%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-f42e9a99719f41e48d87e7954b608aba
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927593B2

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