Water → 6-{(E)-1-[4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-chlorophenyl]-2-(tetrahydro-2H-pyran-4-yl)ethenyl}-3-cyclopropyl-2-methoxypyridine

HRID 70599

Reaction equation

HRID 70599 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[Cl:19][C:20]1[CH:25]=[C:24](/[C:26](/[C:34]2[CH:39]=[CH:38][C:37]([CH:40]3[CH2:42][CH2:41]3)=[C:36]([O:43][CH3:44])[N:35]=2)=[CH:27]\[CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH:23]=[CH:22][C:21]=1[OH:45].O>CN(C)C=O>[Si:12]([O:11][CH2:10][CH2:9][CH2:8][O:45][C:21]1[CH:22]=[CH:23][C:24](/[C:26](/[C:34]2[N:35]=[C:36]([O:43][CH3:44])[C:37]([CH:40]3[CH2:41][CH2:42]3)=[CH:38][CH:39]=2)=[CH:27]\[CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[CH:25][C:20]=1[Cl:19])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 673963982-chloro-4-[(E)-1-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(tetrahydro-2H-pyran-4-yl)ethenyl]phenol

Product 1

HCID 674003536-{(E)-1-[4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-chlorophenyl]-2-(tetrahydro-2H-pyran-4-yl)ethenyl}-3-cyclopropyl-2-methoxypyridineYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

Potassium carbonate (214 mg) and (3-bromopropoxy)(tert-butyl)dimethylsilane (240 μL) were added to a solution of 2-chloro-4-[(E)-1-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(tetrahydro-2H-pyran-4-yl)ethenyl]phenol obtained in Example 1-53(2) (200 mg) in N,N-dimethylformamide (4 mL), and the mixture was stirred at 65° C. for 1.5 hours and at room temperature overnight. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1) to give 6-{(E)-1-[4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-chlorophenyl]-2-(tetrahydro-2H-pyran-4-yl)ethenyl}-3-cyclopropyl-2-methoxypyridine as a colorless oil (245 mg, 80%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was then evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1)

Sources & evidence

ORD record
ord-c7a8ce3299d84ca8b23bcc92f6b6c356
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Linked notes

Loading…