Triphenylphosphine → 2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

HRID 1627288Notes

Reaction equation

HRID 1627288 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([SH:23])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:24][CH3:25].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Si:45]([O:52][CH2:53][CH2:54][O:55][C:56]1[CH:61]=[C:60]([F:62])[C:59]([CH2:63]O)=[C:58]([F:65])[CH:57]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Si:45]([O:52][CH2:53][CH2:54][O:55][C:56]1[CH:57]=[C:58]([F:65])[C:59]([CH2:63][S:23][C:14]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:24][CH3:25])[CH:4]=3)([CH3:10])[CH3:9])=[CH:12][N:13]=2)=[C:60]([F:62])[CH:61]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 66740670(4-(2-(Tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorophenyl)methanolHCID 1784900045-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol

Product 1

HCID 667406352-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazoleYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol (400 mg, 1.06 mmol) in anhyd THF (1.2 mL) were added PPh3 (347 mg, 1.32 mmol), (4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorophenyl)methanol (458 mg, 1.37 mmol) and DIAD (275 μL, 1.32 mmol). The reaction was stirred for 24 h and monitored by LCMS. The reaction mixture was partitioned in EtOAc and H2O. The organic layer was washed with brine, concentrated under reduced pressure, and purified by flash chromatography (45% EtOAc/Hex) to give 2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (620 mg, 87%). MS (EI) m/z 677.40 (MH+).

Workup

  1. customThe reaction mixture was partitioned in EtOAc
  2. washThe organic layer was washed with brine
  3. concentrationconcentrated under reduced pressure
  4. custompurified by flash chromatography (45% EtOAc/Hex)

Sources & evidence

ORD record
ord-d7f4d1a68b804e2581598320345f7871
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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