2-Thiophenecarboxaldehyde → N-[(Thiophen-2-yl)methyl]ethanamine

Temperature

0 °C

To a 0° C. chilled round bottom flask was added ethyl amine hydrochloride (4.58 g, 56.17 mmol) and thiophene-2-carbaldehyde (5.0 mL, 53.50 mmol) in methanol (20.0 mL), followed by triethylamine (7.83 mL, 56.17 mmol) and the reaction was stirred for 30 minutes. Sodiumtriacetoxyborohydride (15.87 g, 74.90 mmol) was added in one portion under vigorous stirring. The ice bath was removed and the flask was attached to a bubbler to allow gas evolution and expansion. The reaction was stirred overnight at room temp. Most of the volatiles were evaporated in vacuo. The reaction mixture was quenched by adding 1 N NaOH, and the product was extracted with dichloromethane. The organic extract was washed with brine and dried over MgSO4. The volatiles were evaporated to give the crude free base N-(thiophen-2-ylmethyl)ethanamine (5.85 g, 41.42 mmol, 77%), which resulted of a purity grade >97% by 1H-NMR analysis, therefore it was used in the next step without any further purification. 1H NMR (400 MHz, CDCl3) δ 1.13 (t, J=7.1 Hz, 3H), 2.71 (q, J=7.2 Hz, 2H), 4.00 (d, J=0.7 Hz, 2H), 6.90-6.97 (m, 2H), 7.21 (dd, J=5.0, 1.3 Hz, 1H).

1. customThe ice bath was removed
2. stirringThe reaction was stirred overnight at room temp
3. customMost of the volatiles were evaporated in vacuo
4. customThe reaction mixture was quenched
5. additionby adding 1 N NaOH
6. extractionthe product was extracted with dichloromethane
7. extractionThe organic extract
8. washwas washed with brine
9. dry with materialdried over MgSO4
10. customThe volatiles were evaporated

ORD record

ord-c1bcf47686604c33915c9b33f9dea5f2

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394287B2