3,4-dihydro-2H-pyran → Ethyl 4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate

HRID 1766111Notes

Reaction equation

HRID 1766111 reaction equation
[OH:1][CH2:2][C:3]1[N:4]=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[S:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[O:23]1[CH:28]=[CH:27][CH2:26][CH2:25][CH2:24]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl>[O:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[O:1][CH2:2][C:3]1[N:4]=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[S:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 17951856Ethyl 4-(hydroxymethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate

Product 1

HCID 21109583Ethyl 4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylateYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 1-L round-bottom flask equipped with a magnetic stir-bar and a N2 inlet was added Ethyl 4-(hydroxymethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate (42 g, 0.127 moles, 1 eq) and dry CH2Cl2 (300 ml) at room temperature. This was followed by the addition of 3,4-dihydro-2H-pyran (14 ml, 0.152 moles, 1.2 eq) as a neat liquid and pyridinium p-toluenesulfonate (6.4 g, 25.4 mmoles, 20 mol %). The reaction mixture was stirred at room temperature overnight (10 hrs). The volatiles were then removed in vacuo and the residue was purified by flash silica gel chromatography (10% EtOAc/Hexanes to 30% EtOAc/Hexanes) to yield 34 g (64%) of pure title compound.

Workup

  1. customTo a 1-L round-bottom flask equipped with a magnetic stir-bar and a N2 inlet
  2. customThe volatiles were then removed in vacuo
  3. customthe residue was purified by flash silica gel chromatography (10% EtOAc/Hexanes to 30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-2e6de6f1b2ec4096956cf07d796e65e6
Source dataset
uspto-grants-2007_06
Patent number
US07229998B2

Reaction notes

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