Potassium Carbonate → (R)-N-(1-benzylpyrrolidin-3-yl)-2-(4-formyl-3-methoxyphenoxy)acetamide

(R)-(−)-1-Benzyl-3-aminopyrrolidine (5 g, 28 mmol) was dissolved in dichloromethane (10 ml). To this solution, a solution of bromoacetyl chloride (4.55 g, 28 mmol) in dichloromethane (5 ml) was added at room temperature. The mixture was stirred at room temperature for 16 hours. The mixture was filtered, washed with dichloromethane and dried in vacuo to afford 6.8 g (72%) of (3R)-N-(1-benzylpyrrolidin-3-yl)-2-bromoacetamide hydrochloride as a solid which was used directly in the next step. 4-Hydroxy-2-methoxybenzaldehyde (2.05 g , 13 mmol) was dissolved in DMF (7 ml) and potassium carbonate (6.2 g, 45 mmol) was added followed by a suspension of the above (3R)-N-(1-Benzylpyrrolidin-3-yl)-2-bromoacetamide hydrochloride (3.0 g, 9 mmol) in DMF (16 ml). The resulting mixture was stirred at room temperature for 16 hours. The mixture was then partitioned between water (100 ml) and ethyl acetate (30 ml). The aqueous phase was extracted with ethyl acetate (2×20 ml) and the combined organic extracts were washed with saturated sodium chloride (3×15 ml), dried (MgSO4) and concentrated in vacuo. The residue was crystallized from diethyl ether to afford 2.11 g (64%) (R)-N-(1-benzylpyrrolidin-3-yl)-2-(4-formyl-3-methoxyphenoxy)acetamide as a solid. M.p.: 98-101° C.

1. customThe mixture was then partitioned between water (100 ml) and ethyl acetate (30 ml)
2. extractionThe aqueous phase was extracted with ethyl acetate (2×20 ml)
3. washthe combined organic extracts were washed with saturated sodium chloride (3×15 ml)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe residue was crystallized from diethyl ether

ORD record

ord-27def9f062d0490aabdf418ae2ac27c9

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06613942B1