Cesium carbonate → Ethyl 2-methyl-2-{4-[({4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)sulfanyl]phenoxy}propanoate

HRID 270148Notes

Reaction equation

HRID 270148 reaction equation
Cl[CH2:2][C:3]1[S:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[N:5][C:4]=1[CH2:18][O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:32][C:33]([O:40][C:41]1[CH:46]=[CH:45][C:44]([SH:47])=[CH:43][CH:42]=1)([CH3:39])[C:34]([O:36][CH2:37][CH3:38])=[O:35]>CC#N>[CH3:39][C:33]([O:40][C:41]1[CH:42]=[CH:43][C:44]([S:47][CH2:2][C:3]2[S:7][C:6]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=3)=[N:5][C:4]=2[CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)=[CH:45][CH:46]=1)([CH3:32])[C:34]([O:36][CH2:37][CH3:38])=[O:35]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 17951841Ethyl 2-methyl-2-(4-sulfanylphenoxy)propanoateHCID 211094595-(chloromethyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole

Product 1

HCID 21109568Ethyl 2-methyl-2-{4-[({4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)sulfanyl]phenoxy}propanoateYield 100%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a 250ml round-bottom flask equipped with a magnetic stir-bar and N2inlet was added 5-(chloromethyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole (7.87g, 20.09mmoles, 1eq) and dry CH3CN (100ml, 0.27M). Solid cesium carbonate (16.4g, 50.22mmoles, 2.5eq) was added all at once followed by the quick addition of ethyl 2-methyl-2-(4-sulfanylphenoxy)propanoate (5.79g, 24.11mmoles, 1.2eq) in dry CH3CN (10ml). The reaction was allowed to stir at room temperature for 2hours at which point the solvent was removed under reduced pressure. The resulting residue was partitioned between EtOAc and 1N NaOH. After the phases were separated the organic fraction washed with H2O, brine and dried over Na2SO4. After filtration the volatiles were removed in vacuo to yield the titled compound in >100% yield. Sometimes because of the difficult separation between the thiophenol and the product, the crude product was carried forward without purification.

Workup

  1. customTo a 250ml round-bottom flask equipped with a magnetic stir-bar
  2. customwas removed under reduced pressure
  3. customThe resulting residue was partitioned between EtOAc and 1N NaOH
  4. customAfter the phases were separated the organic fraction
  5. washwashed with H2O, brine
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the volatiles
  8. customwere removed in vacuo

Sources & evidence

ORD record
ord-9b223631228940e0b1ff6c37bd768d6d
Source dataset
uspto-grants-2008_11
Patent number
US07449468B2

Reaction notes

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