Hydrochloric Acid → HCID 10892999, compound

HRID 1831005Notes

Reaction equation

HRID 1831005 reaction equation
C(C1C=CC(C=CC(O)=O)=CC=1)=O.Cl.[NH2:15][CH2:16][CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1.[CH3:27][O:28][C:29](=[O:40])[CH:30]=[CH:31][C:32]1[CH:37]=[CH:36][C:35]([CH:38]=O)=[CH:34][CH:33]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.ClC(Cl)C.C([O-])([O-])=O.[K+].[K+]>[CH3:27][O:28][C:29](=[O:40])/[CH:30]=[CH:31]/[C:32]1[CH:33]=[CH:34][C:35]([CH2:38][NH:15][CH2:16][CH2:17][C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:20][CH:19]=2)=[CH:36][CH:37]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1150TryptamineHCID 980772-Propenoic acid, 3-(4-formylphenyl)-HCID 5049666Sodium triacetoxyborohydrideHCID 53401287Methyl 3-(4-formylphenyl)-2-propenoate

Product 1

HCID 10892999HCID 10892999, compoundYield 86.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 63651,1-DichloroethaneSolventHCID 11430Potassium CarbonateSolvent

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. temperatureThe resulting suspension is heated
  2. temperatureto reflux for 3 hours
  3. temperaturecooled
  4. customevaporated to dryness
  5. dissolutionThe resulting yellow solid is dissolved in EtOAc
  6. washthe solution washed with saturated NaHCO3
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customto give a pale yellow solid which
  10. customis used without further purification (25.0 g, 92%)
  11. customthe organic phase separated
  12. extractionthe aqueous solution extracted with CH2Cl2
  13. dry with materialThe combined organic extracts are dried (Na2SO4)
  14. customevaporated
  15. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-63492cf11df6403eb134fae171c4a2c7
Source dataset
uspto-grants-2006_06
Patent number
US07067551B2

Reaction notes

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