2-Trimethylsilanyloxy-acrylic acid ethyl ester → 4-(5-Fluoro-2-methoxyphenyl)-4-methyl-2-oxopentanoic acid ethyl ester

HRID 458123Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH3:13])=[C:6]([C:8](O)([CH3:10])[CH3:9])[CH:7]=1.[CH2:14]([O:16][C:17](=[O:25])[C:18]([O:20][Si](C)(C)C)=[CH2:19])[CH3:15]>C(Cl)Cl>[CH2:14]([O:16][C:17](=[O:25])[C:18](=[O:19])[CH2:20][C:8]([C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:12][CH3:13])([CH3:10])[CH3:9])[CH3:15]

Participants

Conditions

Temperature: -78 °C

Procedure

Stannic chloride (5 mL of 1 M solution in methylene chloride, 5 mmol) was added to a stirred solution of 2-(5-fluoro-2-methoxyphenyl)propan-2-ol (2.85 g, 15.5 mmol) and 2-trimethylsilanyloxy-acrylic acid ethyl ester (23.3 mmol, 4.37 g) in anhydrous methylene chloride (45 mL) cooled to −78° C. After 7 hours with the temperature maintained in the range of −78° C. to −50° C., TLC in hexanes-EtOAc (9:1) indicated that a significant amount of starting material remained. More stannic chloride (5 mL of 1 M solution in methylene chloride, 5 mmol) was added with the temperature around −50° C. After 2 hours, all the starting material had been consumed. The reaction mixture was treated with water (100 mL), stirred for 15 minutes and diluted with methylene chloride. The methylene chloride layer was separated, washed with two 50 mL portions of the water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give a light brown oil. The crude product was purified by flash column chromatography over silica gel eluting with 10% EtOAc in hexanes and a fraction corresponding to Rf=0.28 was collected to give the title compound (35%) as a light brown oil.

Workup

temperatureAfter 7 hours with the temperature maintained in the range of −78° C. to −50° C., TLC in hexanes-EtOAc (9:1)
customall the starting material had been consumed
additionThe reaction mixture was treated with water (100 mL)
additiondiluted with methylene chloride
customThe methylene chloride layer was separated
washwashed with two 50 mL portions of the water
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customto give a light brown oil
customThe crude product was purified by flash column chromatography over silica gel eluting with 10% EtOAc in hexanes
customa fraction corresponding to Rf=0.28 was collected

Sources & evidence

ORD record: ord-ddf2a8bfb5f04275b863cc4ca17a175d
Source dataset: uspto-grants-2007_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07189758B2

Reaction notes

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