Investigations of Dithienylglycolic Esters. I. Preparation of Methyl Dithienylglycolates. Magnetically Nonequivalent Protons in Dithienylglycolates.

Discovery of Novel Quaternary Ammonium Derivatives of (3R)-Quinuclidinol Esters as Potent and Long-Acting Muscarinic Antagonists with Potential for Minimal Systemic Exposure after Inhaled Administration: Identification of (3R)-3-{[Hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane Bromide (Aclidinium Bromide)

“…(3R)-1-Azabicyclo[2.2.2]oct-3-yl (2R)-hydroxy(phenyl)2-thienylacetate (36). After five successive crystallizations of compound 34 from boiling isopropanol, an amount of 2.08 g (16%) of diastereomer 36 was obtained.…”

“…Scheme shows the synthesis of (3 R )-quinuclidinol esters with a dithienyl moiety (compounds 19 , 21 , 23 , and 26 ). The reaction of dimethyl oxalate with 2-thienylmagnesium bromide and 3-thienylmagnesium bromide afforded methyl esters 18 and 22 , respectively . Reduction of compound 18 by reaction with stannous chloride in acidic conditions yielded the methyl ester 20 .…”

“…The reaction of dimethyl oxalate with 2-thienylmagnesium bromide and 3-thienylmagnesium bromide afforded methyl esters 18 and 22, respectively. 36 Reduction of compound 18 by reaction with stannous chloride in acidic conditions 37 yielded the methyl ester 20. The reaction of 2-oxopropanoic acid with thiophene in acidic media gave acid 24, 38 which was transformed to its methyl ester 25 by standard methods.…”

Crystal Structures of Tiotropium Bromide and Its Monohydrate in View of Combined Solid-state Nuclear Magnetic Resonance and Gauge-Including Projector-Augmented Wave Studies

“…Tiotropium bromide was obtained using a three-step synthesis according to known methods described previously. [20][21][22] First, dimethyl glioxalate was reacted with 2-thienylmagnesium bromide. Then, the obtained methyl di(2-thienyl)glycolate was subjected to transesterification with scopine hydrobromide in the presence of potassium carbonate to give scopine di(2thienyl)glycolate.…”

Selective synthesis of methyl dithienyl-glycolates

“…In general, synthesis of 1a is carried out via either Friedel-Crafts acylation of thiophene, [19][20][21][22][23][24][25][26][27][28][29] or Grignard reactions. 30 In our hands, reaction of the Grignard reagent derived from 2a with dimethyl oxalate 3 in diethyl ether at reflux afforded 1a in 54% yield, but in inseparable mixture with an impurity identified as the regioisomer 1b (12% yield, Scheme 2); 1b probably derived by equilibration of the initial 2-thienylmagnesium bromide.…”