Tetrabutylammonium Fluoride → tert-Butyl 4-((1-(5-chloro-1H-indazol-7-yl)-2-fluoroethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913949Notes

Reaction equation

HRID 913949 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:14][CH2:15][C:16]3([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH2:12][F:13])[CH:10]=1)[NH:7][N:6](COCC[Si](C)(C)C)[CH2:5]2.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CCOCC>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:14][CH2:15][C:16]3([C:29]4[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=4)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH2:12][F:13])[CH:10]=1)[NH:7][N:6]=[CH:5]2

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67404638Tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)-2-fluoroethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 57546100tert-Butyl 4-((1-(5-chloro-1H-indazol-7-yl)-2-fluoroethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
55 °C

Procedure

Tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)-2-fluoroethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (420 mg, 0.660 mmol) was dissolved in TBAF (1M in THF) (8.5 mL, 8.50 mmol). The flask was sealed and heated at 55° C. for 1.5 h. The reaction was cooled to room temperature and diluted with ether, washed with water then brine, dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (30%-40% EtOAc/Hex) to give title compound (286 mg, 0.565 mmol, 86% yield) as a colorless oil. LC/MS (HPLC method 3): tR=3.78 min, 506.3(MH)+.

Workup

  1. customThe flask was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. washwashed with water
  4. dry with materialbrine, dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography (30%-40% EtOAc/Hex)

Sources & evidence

ORD record
ord-fad7a9f0192446759918fac2cd4b380a
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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