Formic Acid → HCID 18515736, compound

HRID 1276945Notes

Reaction equation

HRID 1276945 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=[CH:9]1)(N1C=CN=C1)=[O:2].C(O)=O.C(NC[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)C.CO>O1CCCC1>[CH:1]([N:8]([CH2:9][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)[CH2:12][CH3:11])=[O:2]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 887MethanolHCID 682631,1'-CarbonyldiimidazoleHCID 14777026HCID 14777026, compound

Product 1

HCID 18515736HCID 18515736, compoundYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of 1,1'-carbonyldiimidazole (326 mmole, 52.81 g) in tetrahydrofuran (164 ml) cooled to 0° C., was added dropwise 96% formic acid (326 mmole, 14.99 g) over a 26 minute period. Reaction stirred at 0° C. for 30 minutes then a light suspension of N-ethyl-p-hydroxyphenethylamine (102 mmole, 16.88 g) in tetrahydrofuran (66 ml) was added over a 10 minute period. Reaction then stirred at 22° C. for 170 minutes before being treated with methanol (10 ml). After stirring for 90 minutes, reaction was concentrated in vacuo to an oil containing crystals. The mixture was taken up into methylene chloride and subjected to preparatory chromatography eluting with a gradient of 0 to 5% methanol methylene chloride over a thirty-minute period. The fractions containing the title compound were combined, concentrated in vacuo to afford 13.46 g of an oil that slowly crystallizes out. Fractions containing title compound and impurities were resubjected to preparatory column chromatography under the same conditions described above to afford an additional 2.61 g of the title compound.

Workup

  1. customReaction
  2. additionwas added over a 10 minute period
  3. customReaction
  4. stirringthen stirred at 22° C. for 170 minutes
  5. stirringAfter stirring for 90 minutes
  6. customreaction
  7. concentrationwas concentrated in vacuo to an oil
  8. additioncontaining crystals
  9. washeluting with a gradient of 0 to 5% methanol methylene chloride over a thirty-minute period
  10. additionThe fractions containing the title compound
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5b6ab76e0b0044f4ac2a6f859922b925
Source dataset
uspto-grants-2000_12
Patent number
US06166216

Reaction notes

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