Imidazole → 6'-bromo-4-(tert-butyldiphenylsilyloxy)spiro[cyclohexane-1,2'-inden]-1'(3'H)-one

HRID 472995Notes

Reaction equation

HRID 472995 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]3)[C:8]2=[O:11])=[CH:4][CH:3]=1.[Si:18](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.N1C=CN=C1>>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([O:17][Si:18]([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:13][CH2:12]3)[C:8]2=[O:11])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 581970336'-Bromo-4-hydroxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one

Product 1

HCID 581981126'-bromo-4-(tert-butyldiphenylsilyloxy)spiro[cyclohexane-1,2'-inden]-1'(3'H)-oneYield 78.4%

Procedure

To a 4 mL vial was placed 6′-bromo-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (41 mg, 0.139 mmol) and it was azeotroped with toluene twice (1 mL/each). The solid was dissolved in DMF (1.5 mL). To this solution was added TBDPS-Cl (40 μL, 0.154 mmol) followed by imidazole (24 mg, 0.353 mmol). The reaction was allowed to stir overnight (˜14 hours) at room temperature. The reaction was quenched with H2O (1 mL) and diluted with diethyl ether (1 mL). The phases were separated and the aqueous phase was back extracted twice with diethyl ether (2 mL/each). The combined organic phases were washed with H2O, brine, dried over Na2SO4, filtered and concentrated. The crude material was purified by flash chromatography (ISCO, 12 g SiO2 cartridge, ethyl acetate/hexanes as the eluents). The corresponding fractions were combined and concentrated under reduce pressure yielding 6′-bromo-4-(tert-butyldiphenylsilyloxy)spiro[cyclohexane-1,2′-inden]-1′(3′H)-one (58 mg, 0.109 mmol, 78% yield). M+H=did not ionized. 1H NMR=(CDCl3, 400 MHz) δ 7.83 (d, J=1.6 Hz 1H), 7.69-7.66 (m, 5H), 7.45-7.32 (m, 7H), 3.73 (m, 1H), 2.98 (s, 2H), 1.93-1.89 (m, 2H), 1.62-1.47 (m, 4H), 1.37 (m, 2H), 1.08 (s, 9H).

Workup

  1. customwas azeotroped with toluene twice (1 mL/each)
  2. dissolutionThe solid was dissolved in DMF (1.5 mL)
  3. customThe reaction was quenched with H2O (1 mL)
  4. additiondiluted with diethyl ether (1 mL)
  5. customThe phases were separated
  6. extractionthe aqueous phase was back extracted twice with diethyl ether (2 mL/each)
  7. washThe combined organic phases were washed with H2O, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by flash chromatography (ISCO, 12 g SiO2 cartridge, ethyl acetate/hexanes as the eluents)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-9d5a9944320d45f28a092fcccd2b00d9
Source dataset
uspto-grants-2014_01
Patent number
US08633212B2

Reaction notes

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