Tetrabutylammonium Fluoride → 3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(3-hydroxypropyl)benzenesulfonamide

HRID 83830Notes

Reaction equation

HRID 83830 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][NH:12][S:13]([C:16]1[CH:21]=[C:20]([F:22])[C:19]([CH2:23][S:24][C:25]2[N:26]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=3)[C:27]([C:30]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([O:40][CH3:41])[CH:34]=3)([CH3:32])[CH3:31])=[CH:28][N:29]=2)=[C:18]([Cl:49])[CH:17]=1)(=[O:15])=[O:14])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:49][C:18]1[CH:17]=[C:16]([S:13]([NH:12][CH2:11][CH2:10][CH2:9][OH:8])(=[O:15])=[O:14])[CH:21]=[C:20]([F:22])[C:19]=1[CH2:23][S:24][C:25]1[N:26]([C:42]2[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=2)[C:27]([C:30]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[C:35]([O:40][CH3:41])[CH:34]=2)([CH3:31])[CH3:32])=[CH:28][N:29]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67236582N-(3-(tert-butyldimethylsilyloxy)propyl)-3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide

Product 1

HCID 867022223-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(3-hydroxypropyl)benzenesulfonamideYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(3-(tert-butyldimethylsilyloxy)propyl)-3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide (1.08 g, 1.44 mmol) in THF (10 mL) was added TBAF (1.0M in THF, 0.7 mL, 1.39 mmol). After stirring 2 h, the reaction was quenched with AcOH (1 mL) and then evaporated in vacuo. The residue was purified by column chromatography (Hex/EtOAc=1:2) to give 3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(3-hydroxypropyl)benzenesulfonamide (0.91 g, 99%). 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J=1.11 Hz, 1H), 7.43 (dd, J=8.41, 1.71 Hz, 1H), 7.15 (s, 1H), 6.56 (dd, J=8.17, 2.21 Hz, 1H), 6.48 (ddd, J=4.63, 3.53, 1.95 Hz, 3H), 3.93 (d, J=1.24 Hz, 2H), 3.78 (s, 3H), 3.64 (t, J=5.63 Hz, 2H), 3.29-3.19 (m, 2H), 1.77-1.69 (m, 2H), 1.51 (s, 7H), 1.30-1.23 (m, 1H), 5.41-5.23 (m, 1H), 6.87 (ddd, J=10.85, 9.87, 5.32 Hz, 3H).

Workup

  1. customthe reaction was quenched with AcOH (1 mL)
  2. customevaporated in vacuo
  3. customThe residue was purified by column chromatography (Hex/EtOAc=1:2)

Sources & evidence

ORD record
ord-39031283277d4efa9ee7c07c030ac242
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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