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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 1766117
Notes
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Reaction equation

HRID 1766117 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 250 ml round-bottom flask equipped with a magnetic stir-bar and N2 inlet was added 5-(chloromethyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole (7.87 g, 20.09 mmoles, 1 eq) and dry CH3CN (100 ml, 0.27M). Solid cesium carbonate (16.4 g, 50.22 mmoles, 2.5 eq) was added all at once followed by the quick addition of ethyl 2-methyl-2-(4-sulfanylphenoxy)propanoate (5.79 g, 24.11 mmoles, 1.2 eq) in dry CH3CN (10 ml). The reaction was allowed to stir at room temperature for 2 hours 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 was 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 250 ml round-bottom flask equipped with a magnetic stir-bar and N2 inlet
  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. washwas washed with H2O, brine
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the volatiles
  8. customwere removed in vacuo

Sources & evidence

ORD record
ord-31f628ae5736404ca981ee22edf5c5cc
Source dataset
uspto-grants-2007_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07229998B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes