Carbon Dioxide → HCID 9880847, compound

HRID 1831006Notes

Reaction equation

HRID 1831006 reaction equation
[OH-:1].[K+].O[NH2:4].Cl.C[O:7][C:8](=O)/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][NH:18][CH2:19][CH2:20][C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][CH:22]=2)=[CH:13][CH:12]=1.ON.C(=O)=O>CO>[OH:1][NH:4][C:8](=[O:7])/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][NH:18][CH2:19][CH2:20][C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][CH:22]=2)=[CH:13][CH:12]=1

Participants

7

Reactant 5

HCID 280Carbon DioxideHCID 787HydroxylamineHCID 14797Potassium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 10892999HCID 10892999, compound

Product 1

HCID 9880847HCID 9880847, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent4×

Procedure

4-formylcinnamic acid methylester is produced by adding 4-formylcinnamic acid (25 g, 0.143 mol) in MeOH and HCl (6.7 g, 0.18 mol). The resulting suspension is heated to reflux for 3 hours, cooled and evaporated to dryness. The resulting yellow solid is dissolved in EtOAc, the solution washed with saturated NaHCO3, dried (MgSO4) and evaporated to give a pale yellow solid which is used without further purification (25.0 g, 92%). To a solution of tryptamine (16.3 g, 100 mmol) and 4-formylcinnamic acid methylester (19 g, 100 mmol) in dichloroethane, NaBH(OAc)3 (21 g, 100 mmol) is added. After 4 hours the mixture is diluted with 10% K2CO3 solution, the organic phase separated and the aqueous solution extracted with CH2Cl2. The combined organic extracts are dried (Na2SO4), evaporated and the residue purified by flash chromatography to produce 3-(4-{[2-(1H-indol-3-yl)-ethylamino]-methyl}-phenyl)-(2E)-2-propenoic acid methyl ester (29 g). A solution of KOH (12.9 g 87%, 0.2 mol) in MeOH (100 mL) is added to a solution of HONH2.HCl (13.9 g, 0.2 mol) in MeOH (200 mL) and a precipitate results. After 15 minutes the mixture is filtered, the filter cake washed with MeOH and the filtrate evaporated under vacuum to approximately 75 mL. The mixture is filtered and the volume adjusted to 100 mL with MeOH. The resulting solution 2M HONH2 is stored under N2 at −20° C. for up to 2 weeks. Then 3-(4-{[2-(1H-indol-3-yl)-ethlamino]-methyl}-phenyl)-(2E)-2-propenoic acid methyl ester (2.20 g, 6.50 mmol) is added to 2 M HONH2 in MeOH (30 mL, 60 mmol) followed by a solution of KOH (420 mg, 6.5 mmol) in MeOH (5 mL). After 2 hours dry ice is added to the reaction and the mixture is evaporated to dryness. The residue is dissolved in hot MeOH (20 mL), cooled and stored at −20° C. overnight. The resulting suspension is filtered, the solids washed with ice cold MeOH and dried under vacuum, producing N-Hydroxy-3-[4-[[[2-(1H-indol-3-yl)-ethyl]-amino]methyl]phenyl]-2E-2-propenamide (m/z 336 [MH+]).

Workup

  1. customa precipitate results
  2. filtrationAfter 15 minutes the mixture is filtered
  3. washthe filter cake washed with MeOH
  4. customthe filtrate evaporated under vacuum to approximately 75 mL
  5. filtrationThe mixture is filtered
  6. customis stored under N2 at −20° C.
  7. customup to 2 weeks
  8. customthe mixture is evaporated to dryness
  9. dissolutionThe residue is dissolved in hot MeOH (20 mL)
  10. temperaturecooled
  11. filtrationThe resulting suspension is filtered
  12. washthe solids washed with ice cold MeOH
  13. customdried under vacuum

Sources & evidence

ORD record
ord-1be151233426430cb8093b5e83d3e43d
Source dataset
uspto-grants-2006_06
Patent number
US07067551B2

Reaction notes

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