Methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate
Founded in 2017, Sigma Chemical Co., Ltd. supplies over 100 countries with high-quality chemicals. We are dedicated to safety, innovation, and global cooperation.
Product Description
Methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate, also known as 4-fluoromethylphenidate (4F-MPH or 4-FMPH), is a fluorinated piperidine ester and a structural analogue of the stimulant drug methylphenidate (Ritalin). It is a derivative of piperidine and has potential applications in central nervous system (CNS) drug discovery. However, its specific uses and safety profile are subject to further scientific research and regulatory approval.
Note: The Methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate chemical raw materials produced by our company are only for scientific research and cannot be used for medical purposes.
Synthesis Methods
-
Synthetic Route: Methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate is synthesized via a multi-step process involving alkylation, hydrolysis, hydrogenation, isomerization, and esterification.
-
Alkylation: (4-Fluorophenyl)acetonitrile is reacted with 2-bromopyridine in the presence of NaNH₂ in toluene to form 2-(4-fluorophenyl)-2-(pyridin-2-yl)acetonitrile.
-
Hydrolysis: The nitrile intermediate is hydrolyzed using concentrated H₂SO₄ to form 2-(4-fluorophenyl)-2-(pyridin-2-yl)acetamide.
-
Hydrogenation: The pyridine ring is reduced to piperidine using Pd/C catalyst in acetic acid, yielding a racemic mixture of erythro and threo diastereomers.
-
Isomerization: The mixture is converted to the threo diastereomer using 50% aq. NaOH.
-
Esterification: The threo amide is hydrolyzed and esterified in one pot using concentrated H₂SO₄ and MeOH, followed by salt formation with isopropanolic HCl.
-
Uses
-
Medicinal Chemistry Intermediate: Methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl)acetate is used as a scaffold resembling pethidine (meperidine) analogs, with fluorine enhancing metabolic stability and lipophilicity.
-
Precursor to Other Compounds: It can be converted to amides, reduced alcohols or aldehydes, and quaternary piperidinium salts.
Properties and Characteristics
-
LogP: ~2.8 (lipophilic, good CNS penetration potential)
-
pKa: ~10.2 (piperidine nitrogen, weakly basic)
-
H-bond Donors: 1 (N-H)
-
H-bond Acceptors: 3 (F, carbonyl O, ether O)
-
Rotatable Bonds: 4
-
Polar Surface Area: ~38 Ų
-
NMR Prediction: Specific peaks for -OCH₃, Piperidine CH-N, -CH(Ar)(COOCH₃), Piperidine CH₂ (ring), and aromatic H atoms.
-
Mass Spectrometry: M⁺ at m/z = 251, base peak at m/z = 84 (piperidine fragment).
Safety and Handling
-
Handling: Treat as a research chemical. Likely irritant to skin and eyes. Assume moderate hazard due to unknown toxicity profile.
-
Storage: Use in a fume hood and wear appropriate personal protective equipment (PPE).
Other Information
-
Legal Note: 4F-MPH is a psychoactive stimulant closely related to methylphenidate and is not approved as a pharmaceutical. It is controlled in some jurisdictions as a methylphenidate analog.