2300174-87-0 | (2R,4R)-4-Fluoro-2-methylpyrrolidine hydrochloride

Packsize	Purity	Availability	Price	Discounted Price
100mg	95%	in stock	$449.00	$315.00
250mg	95%	in stock	$760.00	$532.00
1g	95%	in stock	$1,879.00	$1,316.00

Description

• Catalog Number: BG42356
• Chemical Name: (2R,4R)-4-Fluoro-2-methylpyrrolidine hydrochloride
• CAS Number: 2300174-87-0
• Molecular Formula: C5H11ClFN
• Molecular Weight: 139.5989
• MDL Number: MFCD28390288
• SMILES: F[C@H]1CN[C@@H](C1)C.Cl

Upstream Synthesis Route

The synthesis of (2R,4R)-4-fluoro-2-methylpyrrolidine hydrochloride can be outlined in the following steps:

1. **Start with L-Proline**: Enantiomerically pure (R)-proline can be used as a chiral pool starting material due to its availability and the presence of a pyrrolidine ring.

2. **Alkylation**: Perform a monoalkylation on the nitrogen of the proline using an appropriate methylating agent such as methyl iodide (MeI) in the presence of a base (e.g., NaH or K_2CO_3) to obtain N-methylproline.

3. **Fluorination**: Introduce the fluorine atom at the 4-position of the pyrrolidine ring. This can be done through a halogenation reaction (using Selectfluor or NFSI (N-fluorobenzenesulfonimide)) followed by a dehydrohalogenation to replace the halide with fluorine, resulting in 4-fluoro-N-methylproline.

4. **Reductive Amination**: Utilize a reductive amination strategy to introduce the 2-methyl group. This can be done by reacting 4-fluoroglutaric acid with ammonium acetate and formaldehyde (Eschweiler-Clarke methylation) to provide N-methyl and 2-methyl groups.

5. **Cyclization**: Cyclize the resulting compound to form the pyrrolidine ring. This can involve a cyclization step under reductive conditions such as hydrogenation with a suitable catalyst (e.g., Pd/C) or using a reducing agent like LiAlH_4.

6. **Resolution**: If the stereochemistry is not correct after these steps, a resolution of enantiomers using chiral HPLC or formation of diastereomeric salts with a chiral resolving agent, followed by crystallization, can be employed.

7. **Hydrochloride Formation**: Finally, treat the (2R,4R)-4-fluoro-2-methylpyrrolidine with hydrochloric acid to form the hydrochloride salt.