(1-Benzylpyrrolidin-3-yl)methanol → 1-benzylpyrrolidine-3-carboxylic Acid

A suspension of lithium aluminum hydride (7.50 g) in 150 ml THF was cooled to -5° C. A solution of methyl 1-benzyl-5-oxo-3-pyrrolidine carboxylate (0.064 moles, 15.0 g) in THF was added dropwise. The mixture was heated to 40° C. for 16 hours. Water (25 ml) was added. The mixture was filtered and extracted with ether. The organic phase was washed with water, dried over sodium sulfate and concentrated to yield 11.65 g of N-benzyl-3-hydroxymethylpyrrolidine. (MS) The alcohol (0.06 moles, 11.5 g) in 75 ml 2N sulfuric acid was added dropwise to a stirred solution of chromium dioxide (0.15 moles, 15.0 g) in 100 ml 2N sulfuric acid. The solution was stirred at room temperature for 16 hours. The solution was treated with barium hydroxide hydrate (0.317 mmoles, 100 g) in 250 ml hot water. The solid was filtered and washed with water. The aqueous solution was extracted with ether. Carbon dioxide was bubbled through the solution until the pH was 7.0. The solution was filtered and concentrated to yield 4.5 g of N-benzyl-3-pyrrolidinecarboxylic acid. (MS) The oil was dissolved in 50 ml methanol. Dry HCl gas was bubbled through the solution. The solution was heated to near reflux for 4 hours and concentrated. The residue was neutralized with aqueous sodium bicarbonate. The product was extracted with ether, dried and concentrated to yield 3.0 g of methyl N-benzyl-3-pyrrolidinecarboxylate.

1. filtrationThe solid was filtered
2. washwashed with water
3. extractionThe aqueous solution was extracted with ether
4. customCarbon dioxide was bubbled through the solution until the pH was 7.0
5. filtrationThe solution was filtered
6. concentrationconcentrated

ORD-Eintrag

ord-a15650a63ff24e57a6ad1914c2371bfe

Quelldatensatz

uspto-grants-1996_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05556981