5-Bromo-1-indanone → 5-bromo-1-[(4-{[1-(trifluoromethyl)cyclopropyl]methyl}-1-trityl-1H-imidazol-2-yl)methyl]indan-1-ol

HRID 1881521Notes

Reaction equation

HRID 1881521 reaction equation
C([Li])CCC.[CH3:6][C:7]1[N:8]([C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:9]=[C:10]([CH2:12][C:13]2([C:16]([F:19])([F:18])[F:17])[CH2:15][CH2:14]2)[N:11]=1.[Br:39][C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[C:45](=[O:49])[CH2:44][CH2:43]2>C1COCC1>[Br:39][C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[C:45]([CH2:6][C:7]1[N:8]([C:20]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:9]=[C:10]([CH2:12][C:13]3([C:16]([F:17])([F:18])[F:19])[CH2:14][CH2:15]3)[N:11]=1)([OH:49])[CH2:44][CH2:43]2

Participants

5

Reactant 3

HCID 5206955-Bromo-1-indanoneHCID 591620382-Methyl-4-((1-(trifluoromethyl)cyclopropyl)methyl)-1-trityl-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 667056725-bromo-1-[(4-{[1-(trifluoromethyl)cyclopropyl]methyl}-1-trityl-1H-imidazol-2-yl)methyl]indan-1-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (14.8 mL, 23.7 mmol) was added to a solution of 2-methyl-4-{[1-(trifluoromethyl)cyclopropyl]methyl}-1-trityl-1H-imidazole (7.05 g, 15.8 mmol) in THF (30 mL) at −78° C. After 5 min, a solution of 5-bromoindan-1-one (5 g, 23.7 mmol) in THF (2 mL) was added dropwise to the reaction mixture. The solution was stirred at −78° C. for 2 h. The reaction was quenched with the addition of saturated aqueous NH4Cl. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo to give a residue. The residue was purified by column chromatography eluting with 0-100% EtOAc/hexanes to give 5-bromo-1-[(4-{[1-(trifluoromethyl)cyclopropyl]methyl}-1-trityl-1H-imidazol-2-yl)methyl]indan-1-ol.

Workup

  1. customThe reaction was quenched with the addition of saturated aqueous NH4Cl
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a residue
  7. customThe residue was purified by column chromatography
  8. washeluting with 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-c9187f20ad7b4823907c8bdfd67f91a0
Source dataset
uspto-grants-2012_11
Patent number
US08318767B2

Reaction notes

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