Tin tetrachloride → 2-Methyl-3-{5-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propionyl]-thiophen-2-yl}-2-phenoxy-propionic acid methyl ester

HRID 585272Notes

Reaction equation

HRID 585272 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C:15]([OH:17])=O.C(Cl)(=O)C(Cl)=O.[CH3:24][O:25][C:26](=[O:42])[C:27]([CH3:41])([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH2:28][C:29]1[S:30][CH:31]=[CH:32][CH:33]=1.Cl[Sn](Cl)(Cl)Cl>C(Cl)Cl.CCCCCC.CCOC(C)=O.CN(C=O)C>[CH3:24][O:25][C:26](=[O:42])[C:27]([CH3:41])([O:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[CH2:28][C:29]1[S:30][C:31]([C:15](=[O:17])[CH2:14][CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[O:6][C:2]=2[CH3:1])=[CH:32][CH:33]=1

Participants

9

Reactant 4

HCID 24287Tin tetrachloride2×HCID 65578Oxalyl chlorideHCID 120932643-(5-Methyl-2-phenyl-4-oxazolyl)propionic acidHCID 208231582-Methyl-2-phenoxy-3-thiophen-2-yl-propionic Acid Methyl Ester

Product 1

HCID 208231592-Methyl-3-{5-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propionyl]-thiophen-2-yl}-2-phenoxy-propionic acid methyl esterYield 30%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A sample of 3-(5-methyl-2-phenyl-oxazol-4-yl)-propionic acid (2.27 g, 9.82 mmol) was dissolved in anhydrous CH2Cl2 (20 mL) followed by addition of a catalytic amount of DMF (0.72 mL) and slow addition of a 2 M solution of oxalyl chloride (7.36 mL). The reaction mixture was stirred at room temperature for 24 h under N2. The solvent was removed in vacuo to provide crude acid chloride which was then dissolved in 10 mL anhydrous CH2Cl2 and then added to a flask containing 2-methyl-2-phenoxy-3-thiophen-2-yl-propionic acid methyl ester (527167) (2.51 g, 9.11 mmol) in anhydrous CH2Cl2 (10 mL) at 0° C. under N2. Anhydrous 1.0 M SnCl4 solution (5.6 mL) was then added dropwise at 0° C. After 1 h, the reaction was checked by HPLC, it appeared that little product had formed. Another 3.3 mL of SnCl4 solution was added and allowed to stir for 24 h at room temperature. When the starting materials were consumed, the reaction was quenched by adding 6 M HCl dropwise at 0° C. until solid forms (20 mL) and the aqueous phase was extracted with CH2Cl2 (2×50 mL). The organic layer was washed with water (50 mL) and solvent removed to give an oil. Following column chromatography (gradient 5% to 20% EtOAc in hexane), 1.31 g (30%) of product was obtained: 1H NMR (400 MHz, CDCl3) δ 7.95 (d, 2H), 7.56 (d, 1H), 7.38 (m, 3H), 7.20 (m, 2H), 6.84 (t, 1H), 6.81 (m, 3H), 3.72 (s, 3H), 3.50 (d, 1H), 3.33 (d, 1H), 3.28 (t, 2H), 2.89 (t, 2H), 2.33 (s, 3H), 1.41 (s, 3H); MS (EI) 490.2 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. customto provide crude acid chloride which
  3. additionadded to a flask
  4. waitAfter 1 h
  5. customhad formed
  6. stirringto stir for 24 h at room temperature
  7. customWhen the starting materials were consumed
  8. customthe reaction was quenched
  9. additionby adding 6 M HCl dropwise at 0° C. until solid forms (20 mL)
  10. extractionthe aqueous phase was extracted with CH2Cl2 (2×50 mL)
  11. washThe organic layer was washed with water (50 mL) and solvent
  12. customremoved
  13. customto give an oil

Sources & evidence

ORD record
ord-96a69b07e1334f78bd2ce2a2cf8422be
Source dataset
uspto-grants-2005_08
Patent number
US06930120B2

Reaction notes

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