Tetrahydrofuran → HCID 86757472, compound

HRID 379611Notes

Reaction equation

HRID 379611 reaction equation
[Li]CCCC.CCCCCC.C[Si](C)(C)CCOC[N:18]1[C:22]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)=[C:21]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:20]=[CH:19]1.[F:38][C:39]1[CH:46]=[CH:45][C:42]([CH:43]=O)=[CH:41][CH:40]=1.C1C[O:50]CC1>>[F:35][C:32]1[CH:31]=[CH:30][C:29]([C:21]2[N:20]=[C:19]([CH2:43][C:42]3([OH:50])[CH:45]=[CH:46][C:39]([F:38])=[CH:40][CH2:41]3)[NH:18][C:22]=2[C:23]2[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=2)=[CH:34][CH:33]=1

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 8058HexaneHCID 680234-FluorobenzaldehydeHCID 12044772HCID 12044772, compoundHCID 178418339Butyllithium

Product 1

HCID 86757472HCID 86757472, compoundYield 67%

Procedure

1.6M n-BuLi in hexane (0.085 ml 0.13 mmol) is added at −40° C. to a solution of 1-(2-(trimethylsilyl)ethoxymethyl)-4-(4-fluorophenyl)-5-(4-pyridyl)imidazole (Example 2; 50 mg 0.13 mmol) in THF (1.4 ml). After 15 min at −40° C. 4-fluorobenzaldehyde (0.018 ml 0.18 mmol) in THF (0.4 ml) is addded to the reaction mixture, which is warmed to r.t. and after 10 min. poured on water and extracted 3× with ethyl acetate. The combined organic phases are dried over Na2SO4, evaporated to dryness and render the desired is-protected title compound (64 mg). In order to remove the SEM protecting group, the latter material is dissolved in THF (2 ml), treated with Bu4NF (4.3 ml; 1M in THF) for 1 h at 60° C., poured on a saturated solution of NaHCO3 and extracted 3× with ethyl acetate. The combined organic phases are dried over Na2SO4, evaporated to dryness and chromatographed (SiO2 toluene/EtOH/NH3conc. 90/10/0.6) to yield the title compound as white crystals (32 mg 67% over 2 steps)

Workup

  1. additionpoured on water
  2. extractionextracted 3× with ethyl acetate
  3. dry with materialThe combined organic phases are dried over Na2SO4
  4. customevaporated to dryness
  5. customIn order to remove the SEM
  6. dissolutionthe latter material is dissolved in THF (2 ml)
  7. additiontreated with Bu4NF (4.3 ml; 1M in THF) for 1 h at 60° C.
  8. additionpoured on a saturated solution of NaHCO3
  9. extractionextracted 3× with ethyl acetate
  10. dry with materialThe combined organic phases are dried over Na2SO4
  11. customevaporated to dryness
  12. customchromatographed (SiO2 toluene/EtOH/NH3conc. 90/10/0.6)

Sources & evidence

ORD record
ord-fcf80e6b4d8143b3b1c8177a333031df
Source dataset
uspto-grants-2001_10
Patent number
US06300347B1

Reaction notes

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