Boron trifluoride → 2-Methyl-3-{5-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-thiophen-2-yl}-2-phenoxy-propionic Acid Methyl Ester

HRID 585274Notes

Reaction equation

HRID 585274 reaction equation
C([SiH](CC)CC)C.B(F)(F)F.CCOCC.[CH3:17][O:18][C:19](=[O:51])[C:20]([CH3:50])([O:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH2:21][C:22]1[S:23][C:24]([CH:27](O)[CH2:28][CH2:29][C:30]2[N:31]=[C:32]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[O:33][C:34]=2[CH3:35])=[CH:25][CH:26]=1.B(F)(F)F>C(Cl)Cl>[CH3:17][O:18][C:19](=[O:51])[C:20]([CH3:50])([O:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[CH2:21][C:22]1[S:23][C:24]([CH2:27][CH2:28][CH2:29][C:30]2[N:31]=[C:32]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[O:33][C:34]=2[CH3:35])=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 6356Boron trifluorideHCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 208231613-{5-[1-Hydroxy-3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-thiophen-2-yl}-2-methyl-2-phenoxy-propionic acid methyl ester

Product 1

HCID 208231602-Methyl-3-{5-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-thiophen-2-yl}-2-phenoxy-propionic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of triethylsilane (0.62 mL, 3.89 mmol) in CH2Cl2 (4 mL) at −20° C., boron trifluoride diethyl etherate (0.49 mL, 3.89 mmol) was added. A solution of 3-{5-[1-hydroxy-3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-thiophen-2-yl}-2-methyl-2-phenoxy-propionic acid methyl ester (650 mg, 1.30 mmol) in CH2Cl2 (4 mL) was then added dropwise to the BF3 solution over 1 h, keeping the temperature at −15° C. The reaction was stirred at 0° C. for 2 h. The reaction was quenched with 1 N NaOH (approx. 3.6 mL) diluted with 1.8 mL of water and the pH was adjusted to pH 4.0 using 1 N HCl and 1 N NaOH. The organic layer was separated and the aqueous layer was further extracted with CH2Cl2 (2×30 mL). The combined organic layers were then washed with 0.1 N HCl (30 mL) and water (2×30 mL). Xylene (15 mL) and NaCl were added and the organics were concentrated to dryness to yield a yellow oil. The product was used in the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 7.95 (d, 2H), 7.37 (m, 4H), 7.20 (m, 1H), 6.96 (t, 1H), 6.84 (d, 2H), 6.60 (dd, 2H), 3.72 (s, 3H), 3.41 (d, 1H), 3.30 (d, 1H), 2.78 (t, 2H), 2.50 (t, 2H), 2.24 (s, 3H), 2.00 (m, 2H), 1.43 (s, 3H); MS (EI) 476.2 (M+H)+.

Workup

  1. customat −15° C
  2. customThe reaction was quenched with 1 N NaOH (approx. 3.6 mL)
  3. additiondiluted with 1.8 mL of water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was further extracted with CH2Cl2 (2×30 mL)
  6. washThe combined organic layers were then washed with 0.1 N HCl (30 mL) and water (2×30 mL)
  7. additionXylene (15 mL) and NaCl were added
  8. concentrationthe organics were concentrated to dryness
  9. customto yield a yellow oil
  10. customThe product was used in the next step without further purification

Sources & evidence

ORD record
ord-0ab8740963514f75b09322748c6a73d4
Source dataset
uspto-grants-2005_08
Patent number
US06930120B2

Reaction notes

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