Cesium carbonate → (+/-)-3-[4-(4'-Trifluoromethyl-biphenyl-3-ylmethoxy)-phenyl]-3-(thiazol-2-yl)-propionic acid

HRID 1993076Notes

Reaction equation

HRID 1993076 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[CH2:12]Cl)=[CH:5][CH:4]=1.[OH:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:32]2[S:33][CH:34]=[CH:35][N:36]=2)[CH2:27][C:28]([O:30]C)=[O:29])=[CH:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC(C)=O>[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:16]=[CH:15][CH:14]=[C:11]([CH2:12][O:19][C:20]3[CH:25]=[CH:24][C:23]([CH:26]([C:32]4[S:33][CH:34]=[CH:35][N:36]=4)[CH2:27][C:28]([OH:30])=[O:29])=[CH:22][CH:21]=3)[CH:10]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 222801383-(4-Trifluoromethylphenyl)-benzyl chlorideHCID 59132778Methyl 3-(4-hydroxyphenyl)-3-(thiazol-2-yl)propanoate

Product 1

HCID 59132613(+/-)-3-[4-(4'-Trifluoromethyl-biphenyl-3-ylmethoxy)-phenyl]-3-(thiazol-2-yl)-propionic acidYield 81.8%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °C

Procedure

Benzyl chloride 2.3 (123 mg, 0.456 mmol) and phenol 53.1 (100 mg, 0.380 mmol) were dissolved in acetone (1 mL) and treated with Cs2CO3 (371 mg, 1.14 mmol). The reaction was stirred at 50° C. for 16 h, filtered and concentrated. The residue was purified by column chromatography (silica gel, 30% to 70% ethyl acetate in hexanes). Eluant containing desired compound was concentrated and dissolved in a THF/MeOH/2N LiOH(aq) (1:1:1) solution (2 mL). The mixture was stirred at room temperature for 90 min., and the solution was poured into 0.65 N HCl(aq.) (2 mL). The aqueous phase was extracted with dichloromethane (3×10 mL) and the combined organic phases were dried over Na2SO4. After filtration and drying, 150 mg (0.311 mmol) of carboxylic acid 53 was obtained. 1H NMR (400 MHz) (CDCl3) δ 7.47-7.77 (m, 9H), 7.24-7.27 (m, 3H), 6.99-7.00 (m, 2H), 5.14 (s, 2H), 4.78 (dd, 1H, J=6.8, 4.4 Hz), 3.47 (dd, 1H, J=12.8, 6.8 Hz), 3.09 (dd, 1H, J=12.8, 4.4 Hz).

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography (silica gel, 30% to 70% ethyl acetate in hexanes)
  4. additionEluant containing desired compound
  5. concentrationwas concentrated
  6. dissolutiondissolved in a THF/MeOH/2N LiOH(aq) (1:1:1) solution (2 mL)
  7. stirringThe mixture was stirred at room temperature for 90 min.
  8. additionthe solution was poured into 0.65 N HCl(aq.) (2 mL)
  9. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  10. dry with materialthe combined organic phases were dried over Na2SO4
  11. filtrationAfter filtration
  12. customdrying

Sources & evidence

ORD record
ord-dbf24c4a16484515a6150d7364039d03
Source dataset
uspto-grants-2010_01
Patent number
US07649110B2

Reaction notes

Loading…