Acetic Acid → HCID 21180268, compound

HRID 1386938Notes

Reaction equation

HRID 1386938 reaction equation
C([N:4]1[C:8]([C:9]2[CH:10]=[C:11](C=CC=2)C=O)=NC(C2C=CC(OC)=CC=2)=N1)C=C.[CH2:25]([N:28]1[C:32]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[N:31][C:30]([C:41]2[CH:42]=[C:43]([CH:46]=[CH:47][CH:48]=2)[CH:44]=O)=[N:29]1)[CH:26]=[CH2:27].N1CCCC1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:72].CCO>C1COCC1.C(O)C>[ClH:72].[CH2:25]([N:28]1[C:32]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[N:31][C:30]([C:41]2[CH:48]=[CH:47][CH:46]=[C:43]([CH2:44][N:4]3[CH2:8][CH2:9][CH2:10][CH2:11]3)[CH:42]=2)=[N:29]1)[CH:26]=[CH2:27]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 21180318HCID 21180318, compoundHCID 21717696HCID 21717696, compoundHCID 21887872Ethanol hydrochloride

Product 1

HCID 21180268HCID 21180268, compoundYield 38.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of mixture of 3-[2-allyl-5-(4-methoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-benzaldehyde and 3-[-allyl-5-(4-methoxy-phenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde (1:1) (60 mg, 0.19 mmol), pyrrolidine (19 μl, 5 0.23 mmol) and acetic acid (13 μl, 0.023 mmol) in THF (5 ml) was stirred for 15 min at r.t then sodium triacetoxyborohydride (59 mg, 0.28 mmol) was added in a single portion. This mixture was allowed to react at r.t. under argon until all the aldehyde had been consumed (ca. 1.5 hr). Saturated aqueous Na2CO3 solution was then added, stirred for 15 min and extracted twice with EtOAc (20 ml). The combined organic phase was dried with Na2SO4 filtered and the solvent evaporated under reduced pressure. The resulting isomeric mixture, obtained as an oil, was chromatographed over SiO2 (Merck 230-400 mesh) using CH2Cl2/(2M NH3 in MeOH) 97:3, to provide the separate regioisomers. The isolated regioisomer was taken up in ethanol and was directly converted to its hydrochloride salt with 1.45N HCl/EtOH at 4° C. Following solvent evaporation the resulting pale yellow foam was dried under high vacuum (0.05 mmHg) at 50° C. for 3 h to afford the title compound (30 mg, 0.07 mmol, 38.8%), MS: m/e=375.5 (M+H+). The regiochemistry of alkylation was established by 1H-NMR, nOe spectroscopy.

Workup

  1. customhad been consumed (ca. 1.5 hr)
  2. additionSaturated aqueous Na2CO3 solution was then added
  3. stirringstirred for 15 min
  4. extractionextracted twice with EtOAc (20 ml)
  5. dry with materialThe combined organic phase was dried with Na2SO4
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe resulting isomeric mixture, obtained as an oil
  9. customwas chromatographed over SiO2 (Merck 230-400 mesh)
  10. customto provide the separate regioisomers
  11. customFollowing solvent evaporation the resulting pale yellow foam
  12. customwas dried under high vacuum (0.05 mmHg) at 50° C. for 3 h

Sources & evidence

ORD record
ord-a63eee5dc9ba424ba54c85b3ee1580f1
Source dataset
uspto-grants-2001_07
Patent number
US06265426B1

Reaction notes

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