Iodine → HCID 18382873, compound

In a 500 mL round-bottomed flask 120 mL of tetrahydrofuran and with 13 grams of 4-chloro-thieno[3,2-d]pyridine (76.6 mmol) were cooled to −78° C. To the stirring solution was added n-butyllithium (191.6 mmol, 2.5M in hexane) was added dropwise over a 20 minute period. After stirring an additional 20 minutes iodine (48.3 g, 191.6 mmol) in 80 mL of THF was added dropwise such that the internal temperature did not exceed −78° C. After the addition was complete the reaction was allowed to slowly warm to room temperature. The reaction mixture was quenched by diluting with chloroform and extracting with H2O (2×250 mL), followed by extraction of the combined aqueous material with CHCl3 (1×100 mL). The organic portions were then washed with Na2S2O3 (2×200 mL), H2O (2×200 mL), dried over MgSO4, filtered and dried. The resulting residue was suspended in a minimal amount of chloroform and an excess of ether was added. The solid obtained was filtered and washed with ether. The mother liquor was concentrated and another crop of material was isolated in the same fashion. The two crops of crystals were combined to afford 11.8 g (52%) of 6-iodo-4-chloro-thieno[3,2-d]pyridine that was greater than 90% pure. 1H NMR (400 MHz, CDCl3) δ8.51 (d, 1H), 7.83 (s, 1H), 7.24 (d, 1H). LC-MS: 295.9, 297.9 (MH+); HPLC RT: 6.45 min.

1. additionwas added dropwise over a 20 minute period
2. additionwas added dropwise such that the internal temperature
3. customdid not exceed −78° C
4. additionAfter the addition
5. customThe reaction mixture was quenched
6. additionby diluting with chloroform
7. extractionextracting with H2O (2×250 mL)
8. extractionfollowed by extraction of the combined aqueous material with CHCl3 (1×100 mL)
9. washThe organic portions were then washed with Na2S2O3 (2×200 mL), H2O (2×200 mL)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customdried
13. additionan excess of ether was added
14. customThe solid obtained
15. filtrationwas filtered
16. washwashed with ether
17. concentrationThe mother liquor was concentrated
18. customanother crop of material was isolated in the same fashion

ORD record

ord-31d76bf50a664f34ba61c6b36a68c03c

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492383B1