Tetrahydrofuran → HCID 68500245, compound

HRID 888363Notes

Reaction equation

HRID 888363 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([CH:15]=[CH2:16])[CH:12]=[C:11]([C:17]([OH:19])=O)[CH:10]=1.C(C1N[CH:29]=[CH:30][N:31]=1)(C1NC=CN=1)=O.[CH2:32]1COCC1>>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([CH:15]=[CH2:16])[CH:12]=[C:11]([C:17]([NH:31][CH:30]([CH3:32])[CH3:29])=[O:19])[CH:10]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 68501367HCID 68501367, compound

Product 1

HCID 68500245HCID 68500245, compoundYield 84%

Conditions

Temperature
0 °C

Procedure

In a 500 mL flask charged with carboxylic acid from step D (12 g, 46.8 mmol) in THF (300 mL) at 0° C. was added carbonyl diimidazole (9.1 g, 56.2 mmol) portionwise. Upon complete addition (10 min.) the ice bath was removed and the reaction stirred for 1 h. At this time the mixture was re-cooled to 0° C. and isopropylamine added dropwise (4.98 g, 84 mmol). The mixture was warmed to rt and the reaction complete within 2 h as indicated by LC-MS. The mixture was concentrated and treated with EtOAc and aq. Na2HCO3. The organic layer was washed with brine; dried over Na2SO4 and concentrated to via rotary evaporation and further dried in vacuo. The crude product was re-crystallized from EtOAc/hexanes to give 11.7 g of final product as a colorless solid (84%): LC-MS (M+H)=298.0.

Workup

  1. customwas removed
  2. additionisopropylamine added dropwise (4.98 g, 84 mmol)
  3. temperatureThe mixture was warmed to rt
  4. customthe reaction complete within 2 h
  5. concentrationThe mixture was concentrated
  6. additiontreated with EtOAc and aq. Na2HCO3
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated to via rotary evaporation
  10. customfurther dried in vacuo
  11. customThe crude product was re-crystallized from EtOAc/hexanes

Sources & evidence

ORD record
ord-614d16e661a64a5eab1a9fc83fe9c069
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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