Pyridine → N-allyl-5-chlorothiophenecarboxamide

Temperature

-20 °C

Part A: To a cooled (−30° C.) solution of 16.26 g (0.1 mol) of 5-chlorothiophene-2-carboxylic acid in 75 ml of CH2Cl2 were added 0.15 mol (75 mL, 1.5 eq) of oxalyl chloride 2M solution in CH2Cl2 followed by 4 drops of DMF. The mixture was stirred for 1.5 h. Volatiles were evaporated to yiled the acid chloride as a yellow oil. The crude acid chloride obtained (0.1 mol) was mixed with 41 mL of pyridine and 41 mL of THF. The mixture was cooled to −20° C. and 7.5 mL (0.1 mol) of allylamine was added. The temperature was allowed to increase to ambient and stirring continued for 3 h. Volatiles were evaporated and 300 mL of water added. The yellow precipitate was collected and washed with water. Purified by ISCO system flash chromatography (120 g cartridge loading with CH2Cl2 gradient elution 0% to 100% B over 30 min; (A=CH2Cl2, B=10% MeOH)) to yield 15.7 mg of the N-allyl-5-chlorothiophene-2-carboxamide as a solid. TR=2.67 min (Shimadzu Phenomenex S5 ODS 4.6×50 mm Luna flow rate 2.5 ml/mn; detection at 220 nM; gradient elution 0% to 100% B over 4 min; (A=10% MeOH, 90% H2O, 0.2% H3PO4& B=90% MeOH, 10% H2O, 0.2% H3PO4).

1. customVolatiles were evaporated to yiled the acid chloride as a yellow oil
2. customThe crude acid chloride obtained (0.1 mol)
3. temperatureto increase to ambient and
4. stirringstirring
5. waitcontinued for 3 h
6. customVolatiles were evaporated
7. addition300 mL of water added
8. customThe yellow precipitate was collected
9. washwashed with water
10. customPurified by ISCO system flash chromatography (120 g cartridge loading
11. washwith CH2Cl2 gradient elution 0% to 100% B over 30 min

ORD record

ord-03fc8f5969c0474191f70db8d62af5a0

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07122557B2