Tetrabutylammonium Fluoride → 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanol

HRID 83843Notes

Reaction equation

HRID 83843 reaction equation
[Si]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:43]=[C:42]([F:44])[C:15]([CH2:16][S:17][C:18]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:20]([C:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([O:33][CH3:34])[CH:27]=3)([CH3:25])[CH3:24])=[CH:21][N:22]=2)=[C:14]([F:45])[CH:13]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(Cl)Cl>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:23]([C:20]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:18]([S:17][CH2:16][C:15]3[C:14]([F:45])=[CH:13][C:12]([O:11][CH2:10][CH2:9][OH:8])=[CH:43][C:42]=3[F:44])=[N:22][CH:21]=2)([CH3:25])[CH3:24])=[CH:27][C:28]=1[O:33][CH3:34]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 667406352-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

Product 1

HCID 667407372-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanolYield 79.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (440 mg, 0.65 mmol, 1.0 eq) in anhyd DCM was added tetrabutylammonium fluoride (2.9 mL, 2.9 mmol, 4.4 eq, 1.0 M in THF). After stirring 16 h, the reaction was quenched with satd NaHCO3 and extracted with DCM. The combined extracts were washed with water and brine, dried, concentrated and purified (silica, 0 to 80% EtOAc/Hex) to yield 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenoxy)ethanol (290 mg, 79%) as a white foam: 1H NMR (400 MHz, CDCl3) δ 7.18 (d, J=7.8 Hz, 1H), 7.06 (d, J=8.2 Hz, 1H), 6.74-6.63 (m, 2H), 6.46-6.33 (m, 2H), 6.33-6.20 (m, 4H), 4.03 (s, H), 3.90 (dt, J=8.7, 4.1 Hz, 4H), 3.68 (s, 3H), 1.39 (s, 6H).

Workup

  1. customthe reaction was quenched with satd NaHCO3
  2. extractionextracted with DCM
  3. washThe combined extracts were washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. custompurified (silica, 0 to 80% EtOAc/Hex)

Sources & evidence

ORD record
ord-667cf50a12ae4a8fb9e5cfa6e7225ec4
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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