tert-Butyl 4-(((5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate → tert-Butyl 4-phenyl-4-(((1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate

HRID 913819Notes

Reaction equation

HRID 913819 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:11][O:12][CH2:13][C:14]3([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[CH:10]=1)[N:7]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:6]=[CH:5]2.C([Li])(C)(C)C>O1CCCC1>[C:27]1([C:14]2([CH2:13][O:12][CH2:11][C:9]3[CH:10]=[CH:2][CH:3]=[C:4]4[C:8]=3[N:7]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:6]=[CH:5]4)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

4

Reactant 2

HCID 57545925tert-Butyl 4-(((5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 57545951tert-Butyl 4-phenyl-4-(((1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 4-(((5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (55 mg, 0.09 mmol) was dissolved in dry tetrahydrofuran (1.5 mL) and stirred at room temperature for 15 min. The stirred mixture was cooled to −78° C. and treated with a solution of tert-butyllithium (1.7M in pentane, 103 μL, 0.17 mmol) over several minutes. The mixture was stirred at −78° C. for 20 min, quenched by addition of a few drops of methanol and concentrated. Flash chromatography on silica gel (20% ethyl acetate/hexanes) afforded 34 mg (91%) as a clear oil. 1H-NMR (CDCl3, 300 MHz) δ 7.93 (s, 1H), 7.66 (dd, J=7.0, 1.1 Hz, 1H), 7.04-7.23 (m, 7H), 5.38 (s, 2H), 4.70 (s, 2H), 3.39 (s, 2H), 3.35-3.41 (m, 2H), 2.94-3.03 (m, 2H), 2.05-2.09 (m, 2H), 1.71-1.80 (m, 2H), 1.39 (s, 9H), 0.72-0.78 (m, 2H), 0.14 (s, 9H). Mass spec.: 552.15 (MH)+.

Workup

  1. temperatureThe stirred mixture was cooled to −78° C.
  2. stirringThe mixture was stirred at −78° C. for 20 min
  3. customquenched by addition of a few drops of methanol
  4. concentrationconcentrated
  5. customFlash chromatography on silica gel (20% ethyl acetate/hexanes) afforded 34 mg (91%) as a clear oil

Sources & evidence

ORD record
ord-0d59247ea53648d990434cbcc691f3dc
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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