Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl ester → HCID 12966849, compound

HRID 2417101Notes

Reaction equation

HRID 2417101 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([O:14][C:15]([CH3:20])([CH3:19])[C:16]([OH:18])=[O:17])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:7]=1.[CH3:21][C:22]1[O:26][C:25]([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:29][CH:28]=2)=[N:24][C:23]=1[CH2:39][CH2:40]OS(C1C=CC(C)=CC=1)(=O)=O>CCO>[C:30]1([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:31]=[CH:32][C:27]([C:25]2[O:26][C:22]([CH3:21])=[C:23]([CH2:39][CH2:40][O:1][C:2]3[CH:3]=[CH:4][C:5]([O:14][C:15]([CH3:20])([CH3:19])[C:16]([OH:18])=[O:17])=[C:6]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[CH:7]=3)[N:24]=2)=[CH:28][CH:29]=1

Participants

4

Reactant 2

HCID 12966835Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl esterHCID 22633482HCID 22633482, compound

Product 1

HCID 12966849HCID 12966849, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
67.5 °C

Procedure

A mixture of 2-(5-hydroxy-biphenyl-2-yloxy)-2-methyl-propionic acid (80 mg, 0.26 mmol), toluene-4-sulfonic acid 2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethyl ester (0.22 mmol) (see Ex. 1, part F), and 1,5,7-triazobicyclo[4.4.0]dec-5-ene bound to polystyrene (200 mg, 2.6 mmol/g resin, Fluka) was diluted with absolute EtOH (2 mL) and was heated at 65-70° C. for 20 h. The warm mixture was filtered through a cotton plug, and the resin was washed with EtOH (2 mL). The combined filtrates were treated with aqueous 5N NaOH (0.3 mL), heated at 55° C. for 1.5 h, cooled to ambient temperature, and concentrated in vacuo. The residue was treated with ice water (1 mL) and acidified with 5N aqueous HCl (0.5 mL). The mixture with CH2Cl2 (1 mL) was transferred to a ChemElute cartridge (3 g) and eluted with CH2Cl2. The eluent was concentrated to crude product which was purified by mass guided HPLC to afford a white foam. 1H NMR (400 MHz, CDCl3) δ 1.26 (s, 6H), 2.44 (s, 3H), 3.10 (t, 2H, J=5.9 Hz), 4.28 (t, 2H, J=6.1 Hz), 6.81 (dd, 1H, J=2.9, 8.8 Hz), 6.86 (d, 1H, J=2.9 Hz), 7.01 (d, 1H, J=8.8 Hz), 7.30-7.48 (m, 8H), 7.63 (d, 2H, J=7.3 Hz), 7.70 (d, 2H, J=8.3 Hz), 8.11 (d, 2H, J=8.3 Hz); MS (ES) m/e [M−1].

Workup

  1. filtrationThe warm mixture was filtered through a cotton plug
  2. washthe resin was washed with EtOH (2 mL)
  3. additionThe combined filtrates were treated with aqueous 5N NaOH (0.3 mL)
  4. temperatureheated at 55° C. for 1.5 h
  5. temperaturecooled to ambient temperature
  6. concentrationconcentrated in vacuo
  7. additionThe residue was treated with ice water (1 mL)
  8. washeluted with CH2Cl2
  9. concentrationThe eluent was concentrated to crude product which
  10. customwas purified by mass
  11. customto afford a white foam

Sources & evidence

ORD record
ord-145805fa99544711a298762c72932a99
Source dataset
uspto-grants-2004_11
Patent number
US06825222B2

Reaction notes

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