Chloromethyl Methyl Ether → HCID 122643080, compound

HRID 1424839Notes

Reaction equation

HRID 1424839 reaction equation
[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]

Participants

8

Reactant 5

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 122643076HCID 122643076, compound

Product 1

HCID 122643080HCID 122643080, compoundYield 85.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-f42e9a99719f41e48d87e7954b608aba
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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