1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-Methyl-2-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid ethyl ester

HRID 1269533Notes

Reaction equation

HRID 1269533 reaction equation
C(O)(=O)[C@@H]([C@H](C(O)=O)O)O.[CH2:11]([O:13][C:14](=[O:32])[C:15]([CH3:31])([O:17][C:18]1[CH:23]=[C:22]([CH:24]2[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]2)[CH:21]=[CH:20][C:19]=1[CH3:30])[CH3:16])[CH3:12].CN(C)CCCN=C=NCC.[CH3:44][C:45]1[N:46]=[C:47]([C:53]2[CH:58]=[CH:57][C:56]([C:59]([F:62])([F:61])[F:60])=[CH:55][CH:54]=2)[S:48][C:49]=1[C:50](O)=[O:51]>C(OCC)(=O)C.C(OCC)C>[CH2:11]([O:13][C:14](=[O:32])[C:15]([CH3:31])([O:17][C:18]1[CH:23]=[C:22]([CH:24]2[CH2:29][CH2:28][CH2:27][N:26]([C:50]([C:49]3[S:48][C:47]([C:53]4[CH:54]=[CH:55][C:56]([C:59]([F:62])([F:60])[F:61])=[CH:57][CH:58]=4)=[N:46][C:45]=3[CH3:44])=[O:51])[CH2:25]2)[CH:21]=[CH:20][C:19]=1[CH3:30])[CH3:16])[CH3:12]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27756634-Methyl-2-(4-(trifluoromethyl)phenyl)-5-thiazolecarboxylic acidHCID 688846382-Methyl-2-(2-methyl-5-piperidin-3-yl-phenoxy)-propionic acid ethyl ester l-tartaric acid salt

Product 1

HCID 688866962-Methyl-2-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid ethyl esterYield 91.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-methyl-2-(2-methyl-5-piperidin-3-yl-phenoxy)-propionic acid ethyl ester L-tartaric acid salt (155 mg, 0.34 mmol) was dissolved in 50 mL ethyl acetate and washed with 50 mL saturated aqueous NaHCO3. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The resultant oil was taken up in 2 mL CH2Cl2 and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (130 mg, 0.68 mmol) and 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylic acid (98 mg, 0.34 mmol) were added. The reaction was stirred at ambient temperature under nitrogen for 72 h. The reaction was diluted with 100 mL diethyl ether and washed with water (100 mL), 0.5 N HCl (2×100 mL), saturated aqueous NaHCO3 (2×100 mL), dried over Na2SO4 and concentrated under reduced pressure to yield 2-methyl-2-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid ethyl ester (179 mg, 91%) as a clear oil.

Workup

  1. washwashed with 50 mL saturated aqueous NaHCO3
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. washwashed with water (100 mL), 0.5 N HCl (2×100 mL), saturated aqueous NaHCO3 (2×100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5bf6272fe6ad43c4a1f8e8e2af6ed55e
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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