Dimethylformamide → 3-{4-[2-(2-Cyclohexyl-5-methyloxazol-4-yl)ethoxy]-2-phenoxymethylphenyl}propionic acid

HRID 1181130Notes

Reaction equation

HRID 1181130 reaction equation
C([O:5][C:6](=[O:25])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21]C=1)(C)(C)C.[C:26]1(C2C=CC=CC=2)[CH:31]=[CH:30][C:29]([C:32]2[O:33][C:34]([CH3:50])=[C:35]([CH2:37][CH2:38]OS(C3C=CC(C)=CC=3)(=O)=O)[N:36]=2)=[CH:28][CH:27]=1.CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CCOCC>[CH:29]1([C:32]2[O:33][C:34]([CH3:50])=[C:35]([CH2:37][CH2:38][O:15][C:12]3[CH:13]=[CH:14][C:9]([CH2:8][CH2:7][C:6]([OH:5])=[O:25])=[C:10]([CH2:16][O:17][C:18]4[CH:19]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:11]=3)[N:36]=2)[CH2:28][CH2:27][CH2:26][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 12966835Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl esterHCID 589791133-(2-Benzyloxymethyl-4-hydroxy-phenyl)-propionic acid tert-butyl ester

Product 1

HCID 179845553-{4-[2-(2-Cyclohexyl-5-methyloxazol-4-yl)ethoxy]-2-phenoxymethylphenyl}propionic acidYield 78.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

General procedure for the parallel synthesis of analogs using the DynaVac Carousel apparatus: A 50 mL glass tube with screw cap and nitrogen inlet was charged with 3-(2-benzyloxymethyl-4-hydroxy-phenyl)-propionic acid tert-butyl ester (0.050 g, 0.146 mmol), toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-5-methyloxazol-4-yl)ethyl ester (0.078 g, 0.18 mmol), anhydrous DMF (0.5 mL), and then cesium carbonate (0.072 g, 0.22 mmol). The mixture was stirred at ambient temperature for 16 h. MS analysis of the reaction indicated that the intermediate ester was formed, MS (ES) m/e 534 (M+1). The crude reaction was poured into ether (30 mL), and washed with brine (2×), dried (Na2SO4), and concentrated in vacuo. The crude residue was dissolved in CH2Cl2 (2 mL) and trifluoroacetic acid was added (1.0 mL). The reaction mixture was stirred at ambient temperature for 2 h and was concentrated under a stream of N2. The crude product was purified by mass-directed reverse phase HPLC to provide 0.053 g (71%) of 3-{4-[2-(2-Cyclohexyl-5-methyloxazol-4-yl)ethoxy]-2-phenoxymethylphenyl}propionic acid. MS (ES) m/e 478 (M+1).

Workup

  1. customGeneral procedure for the parallel synthesis of analogs
  2. customA 50 mL glass tube with screw cap
  3. customwas formed
  4. customThe crude reaction
  5. washwashed with brine (2×)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude residue was dissolved in CH2Cl2 (2 mL)
  9. additiontrifluoroacetic acid was added (1.0 mL)
  10. stirringThe reaction mixture was stirred at ambient temperature for 2 h
  11. concentrationwas concentrated under a stream of N2
  12. customThe crude product was purified by mass-directed reverse phase HPLC

Sources & evidence

ORD record
ord-487e68d86ffb4078b44c1ceedfc81735
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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