ChemicalBook CAS DataBase List 3,3-Difluorocyclobutanecarboxylic acid

3,3-Difluorocyclobutanecarboxylic acid synthesis

10synthesis methods

Product Name:3,3-Difluorocyclobutanecarboxylic acid
CAS Number:107496-54-8
Molecular formula:C5H6F2O2
Molecular Weight:136.1

3,3-Difluorocyclobutanecarboxylic acid can be used as organic synthesis intermediate and pharmaceutical intermediate, mainly in laboratory research. It was prepared from 3,3-Difluorocyclobutanecarboxylic acid ethyl ester with NaOH by stirring in a 1:1 mixture of MeOH/H2O for 15 h at room temperature.

681128-38-1 Synthesis

Cyclobutanecarboxylic acid, 3,3-difluoro-, ethyl ester (9CI)

681128-38-1
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107496-54-8
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$29.00/1g

Yield:107496-54-8 98%

Reaction Conditions:

with sodium hydroxide in methanol;water at 20; for 15 h;

Steps:

3,3-Difluorocyclobutane-1-carboxylic Acid (7)
NaOH (10.7 g, 0.268 mol) was dissolved in MeOH (100 mL) and H₂O(100 mL). Ester 23 (40.0 g, 0.244 mol) was added at r.t., and the resulting mixture was stirred at r.t. for 15 h, then evaporated in vacuo to half of the volume, acidified with concd aq HCl to pH 1, and extracted with CH₂Cl₂ (3 × 350 mL). The combined organic extracts were evaporated in vacuo.Yield: 32.4 g (98%); white solid; mp 49-52 °C. ¹H NMR (500 MHz, CDCl₃): δ = 12.11 (br s, 1 H), 3.06-2.96 (m, 1 H), 2.94-2.79 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 179.6, 118.0 (dd, J = 284, 271 Hz), 38.1(t, J = 24.8 Hz), 26.0 (dd, J = 14.0, 5.7 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = -84.5 (d, J = 194 Hz), -97.8 (d, J = 194Hz). GCMS (EI): m/z = 119 [M - OH]+, 97 [M - CO2H]+. Anal. Calcd for C₅H₆F₂O₂: C, 44.13; H, 4.44. Found: C, 43.86; H, 4.42.

References:

Melnykov, Kostiantyn P.;Granat, Dmitriy S.;Volochnyuk, Dmitriy M.;Ryabukhin, Sergey V.;Grygorenko, Oleksandr O. [Synthesis,2018,vol. 50,# 24,art. no. SS-2018-T0427-OP,p. 4949 - 4957]

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