Acetylimidazole diethyl acetal → HCID 68283491, compound

HRID 1855298Notes

Reaction equation

HRID 1855298 reaction equation
C(OC([N:9]1[CH:13]=[CH:12][N:11]=[CH:10]1)(OCC)C)C.[Li]CCCC.[Br:19][C:20]1[CH:33]=[C:32]2[C:23]([O:24][C:25]3[C:26]([F:37])=[CH:27][C:28]([O:35][CH3:36])=[CH:29][C:30]=3[C:31]2=[O:34])=[CH:22][CH:21]=1>C(OCC)C>[Br:19][C:20]1[CH:33]=[C:32]2[C:23]([O:24][C:25]3[C:26]([F:37])=[CH:27][C:28]([O:35][CH3:36])=[CH:29][C:30]=3[C:31]2([C:10]2[NH:9][CH:13]=[CH:12][N:11]=2)[OH:34])=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 145471Acetylimidazole diethyl acetalHCID 574756397-bromo-4-fluoro-2-methoxy-9H-xanthen-9-oneHCID 178418339Butyllithium

Product 1

HCID 68283491HCID 68283491, compoundYield 45.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-40 °C

Procedure

1-(1,1-Diethoxyethyl)-1H-imidazole (7 g, 38.0 mmol) was dissolved in diethyl ether (100 ml) and cooled to −40° C. and n-BuLi (1.6M in hexane) (23.75 ml, 38.0 mmol) was added. The solution was stirred for 10 minutes and 7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-one (Example 5, 6.14 g, 19.00 mmol) was added in one portion. The solution was stirred one hour at −40° C., then allowed to warm to RT for 15 minutes. The solution was quenched with 2 N HCl until at pH 1, stirred for 15 minutes, then made basic with concentrated sodium carbonate and stirred for 15 minutes. The product was collected by filtration. The filtrate was also extracted with EtOAc, the extracts were concentrated and combined with the material collected by filtration. The product was loaded onto silica and purified via silica gel column chromatography (RediSep 80 g column) using 10-50% 90/10/1 (DCM/MeOH/ammonia) in DCM to afford 7-bromo-4-fluoro-9-(1H-imidazol-2-yl)-2-methoxy-9H-xanthen-9-ol (3.4 g, 8.69 mmol) as an off white solid.

Workup

  1. stirringThe solution was stirred one hour at −40° C.
  2. temperatureto warm to RT for 15 minutes
  3. customThe solution was quenched with 2 N HCl until at pH 1
  4. stirringstirred for 15 minutes
  5. stirringstirred for 15 minutes
  6. filtrationThe product was collected by filtration
  7. extractionThe filtrate was also extracted with EtOAc
  8. concentrationthe extracts were concentrated
  9. filtrationcollected by filtration
  10. custompurified via silica gel column chromatography (RediSep 80 g column)

Sources & evidence

ORD record
ord-0a3c93576280430a8902d1acf647aec3
Source dataset
uspto-grants-2015_02
Patent number
US08962859B2

Reaction notes

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