Hydrochloric Acid → HCID 57722994, compound

HRID 1987022Notes

Reaction equation

HRID 1987022 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([Br:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])[C:3]=1[CH2:16][CH2:17][C:18]([OH:20])=O.C[Si](C=[N+]=[N-])(C)C.C[Al](C)C.[Cl:32][C:33]1[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=1[NH2:35].Cl>C1(C)C=CC=CC=1.CO.ClCCl.O>[Cl:32][C:33]1[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=1[NH:35][C:18](=[O:20])[CH2:17][CH2:16][C:3]1[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])=[N:5][C:6]([Br:8])=[CH:7][C:2]=1[Br:1]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 72402-ChloroanilineHCID 167693TrimethylsilyldiazomethaneHCID 16682925TrimethylaluminumHCID 57722977HCID 57722977, compound

Product 1

HCID 57722994HCID 57722994, compoundYield 69%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

3-[4,6-Dibromo-2-(2-chlorophenyl)-3-pyridyl]propionic acid (1.09 g, 2.603 mmol) was dissolved in toluene (25 ml)-methanol (5 ml), and a 2M solution of trimethylsilyl-diazomethane in hexanes added (5 ml), and the solution allowed to stand for about 0.5 hours. The solution was evaporated in vacuo, and the resulting oil re-dissolved in dichloromethane (25 ml). This solution was added slowly at 22° to a trimethylaluminium-2-chloroaniline complex [prepared by adding 2M trimethylaluminium in toluene (2.6 ml) to a solution of 2-chloroaniline (0.55 ml, 5.188 mmol) in dichloromethane (30 ml)] and the solution stirred at 22° for 20 h under nitrogen. Water (15 ml) was added (very slowly at first), followed by sufficient 2M hydrochloric acid to dissolve all the precipitated aluminium salts. The organic phase was separated and the aqueous phase further extracted with dichloromethane (60 ml). The combined organic extracts were dried (Na2SO4), evaporated in vacuo, and the oily residue purified by column chromatography over silica (50 g) eluting with cyclohexane ethyl acetate (100:0-70:30) to afford the title compound as a gum (0.95 g, 69%).

Workup

  1. customThe solution was evaporated in vacuo
  2. dissolutionthe resulting oil re-dissolved in dichloromethane (25 ml)
  3. additionThis solution was added slowly at 22° to a trimethylaluminium-2-chloroaniline complex [
  4. customprepared
  5. customThe organic phase was separated
  6. extractionthe aqueous phase further extracted with dichloromethane (60 ml)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. customevaporated in vacuo
  9. customthe oily residue purified by column chromatography over silica (50 g)
  10. washeluting with cyclohexane ethyl acetate (100:0-70:30)

Sources & evidence

ORD record
ord-ca508a863a41416c875041488f7911a5
Source dataset
uspto-grants-2009_06
Patent number
US07550480B2

Reaction notes

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