Sodium Iodide → (2-(3-Methoxy-propyl)-4-{methyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl ester

HRID 1393099Notes

Reaction equation

HRID 1393099 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH3:14])=[CH:9][C:8]=1[CH2:15][CH2:16][CH2:17][O:18][CH3:19])[CH3:2].[H-].[Na+].[Na+].[I-].Cl[CH2:26][C:27]1[S:31][C:30]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)=[N:29][C:28]=1[CH3:42]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:20])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([CH3:14])[CH2:26][C:27]2[S:31][C:30]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=3)=[N:29][C:28]=2[CH3:42])=[CH:9][C:8]=1[CH2:15][CH2:16][CH2:17][O:18][CH3:19])[CH3:2]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 27830065-Chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-thiazoleHCID 670721342-(3-Methoxy-propyl)-4-methylamino-phenoxy-acetic acid ethyl ester

Product 1

HCID 69220724(2-(3-Methoxy-propyl)-4-{methyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 0.216 g (0.77 mmol) of the above prepared [2-(3-methoxy-propyl)-4-methylamino-phenoxy]-acetic acid ethyl ester, dissolved in 2.4 ml of abs. DMF, were added successively at 0° C. 0.037 g of NaH (60% in mineral oil, 1.2 eq.), 0.115 g (1 eq.) of NaI and 0.215 g (0.96 eq.) of 5-chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole (WO02/28433). The reaction was allowed to proceed for 5 min at 0° C. and for 0.5 h at ambient temperature. Pouring onto crashed ice/aqueous 10% KHSO4, twofold extraction with EtOAc, washing with water and brine, drying over magnesium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/EtOAc=78/22), yielded 0.284 g of the title compound as light yellow oil, MS: 537.5 (MH)+.

Workup

  1. dissolutiondissolved in 2.4 ml of abs
  2. additionPouring
  3. extractionice/aqueous 10% KHSO4, twofold extraction with EtOAc
  4. washwashing with water and brine
  5. dry with materialdrying over magnesium sulfate, and evaporation of the solvents

Sources & evidence

ORD record
ord-d4b0eb115ced4d98ac0b4f86d1ed93cc
Source dataset
uspto-grants-2008_03
Patent number
US07345067B2

Reaction notes

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