Ethyl 2-(diphenylmethyleneamino)acetate → Ethyl alpha-amino-3-methyl-5-oxopyrrolidine-2-pentanoate

Temperature

-72 °C

A solution of N-(diphenylmethylene)glycine ethyl ester (Aldrich, 37 mmol) in THF (20 mL) is added to −72° C. solution of sodium bis (trimethylsilylamide) (35 mmol, 0.5 M in THF), while the solution is kept below −65° C. The resulting solution is then stirred at −72° C. for 30 min.; followed by the rapid addition of a cooled solution (−72° C.) of the product from EXAMPLE 236 (24 mmol) in THF via canula. The cooling bath is removed immediately and the mixture allowed to warm to 0° C. for 4 h. The reaction mixture is partitioned between ether and 10% aqueous sodium bisulfate, then dried and concentrated. The product is purified by column chromatography. This intermediate is then treated with 0.1 N aqueous hydrochloric acid for 3 h, followed by extraction with ether and lyophilization of the aqueous solution, to yield the title material.

1. customis kept below −65° C
2. customThe cooling bath is removed immediately
3. temperatureto warm to 0° C. for 4 h
4. customThe reaction mixture is partitioned between ether and 10% aqueous sodium bisulfate
5. customdried
6. concentrationconcentrated
7. customThe product is purified by column chromatography
8. additionThis intermediate is then treated with 0.1 N aqueous hydrochloric acid for 3 h
9. extractionfollowed by extraction with ether and lyophilization of the aqueous solution

ORD record

ord-f4f1053b188a4bdf962cb363ccdc3d17

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06448286B1