Tetrabutylammonium Fluoride → (+/-)-tert-butyl 4-((1-(5-chloro-3-cyano-1H-indol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913972Notes

Reaction equation

HRID 913972 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[N:7](COCC[Si](C)(C)C)[CH:6]=[C:5]2[C:43]#[N:44].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[C:43]#[N:44]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57546180(+/-)-tert-butyl 4-((1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 57545997(+/-)-tert-butyl 4-((1-(5-chloro-3-cyano-1H-indol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylateYield 71.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (±)-tert-butyl 4-((1-(5-chloro-3-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (406 mg, 0.632 mmol) and TBAF (4 mL, 4.00 mmol) (1M in THF) in THF (10 mL) was heated at reflux for 8 hours then cooled to ambient temperature and the solvent was evaporated. Purified on SiO2 column with 50% ethyl acetate/hexanes to obtain (±)-tert-butyl 4-((1-(5-chloro-3-cyano-1H-indol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (231 mg, 0.451 mmol, 71.4% yield) as a clear foam. 1H-NMR (CDCl3, 400 MHz) δ 8.11 (bs, 1H), 7.57 (d, J=1.9 Hz, 1H), 7.27 (m, 2H), 7.11 (m, 2H), 7.10 (s, 1H), 4.54 (q, J=6.5 Hz, 1H), 3.7 (m, 2H), 3.43(d, J=8.8 Hz, 1H), 3.20 (d, J=8.6 Hz, 1H), 3.10 (t, J=7.5 Hz, 1H), 2.97 (t, J=10.1 Hz, 1H), 2.38 (m, 2H), 1.80-2.00 (m, 2H), 1.64 (m, 1H), 1.40 (s, 3H). LC/MS (HPLC method 4): tR=4.02 min, 534.13(MNa)+.

Workup

  1. temperatureat reflux for 8 hours
  2. customthe solvent was evaporated
  3. customPurified on SiO2 column with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2565c4c0dc49476783a8cbf14901b189
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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