Diisopropylamine → 5-Iodothiophene-2-carboxylic acid

Temperature

0 °C

To a stirred solution of 10.9 mL (78.0 mmol) of freshly distilled diisopropylamine in 150 mL of THF under argon at -78° C. was added 48.7 mL (78.0 mmol) of 1.6 M n-BuLi in hexanes to give a pale yellow solution which was allowed to stir at -78° C. for 10 min when 5.0 g (39.0 mmol) of 2-thiophenecarboxylic acid in 31 mL of THF was added dropwise over 10 min to give a grey-white suspension. The metallation was allowed to proceed for 30 min when 8.77 g (39.0 mmol) of N-iodosuccinimide in 25 mL of THF was added very rapidly to give an orange-yellow solution which was allowed to gradually warm to 0° C. After 0.5 h at 0° C., the brown-yellow mixture was quenched with water, diluted with ether and made acidic by the addition of solid citric acid to give a very dark brown-orange solution. The organic layer was separated and washed with water, saturated NaHSO3, brine, dried over MgSO4 and evaporated to provide 9.5 g (96%) of title acid as a brown-yellow solid which was used directly in the following reaction.

1. customto give a pale yellow solution which
2. additionwas added dropwise over 10 min
3. customto give a grey-white suspension
4. customto give an orange-yellow solution which
5. waitAfter 0.5 h at 0° C.
6. customthe brown-yellow mixture was quenched with water
7. additiondiluted with ether
8. additionmade acidic by the addition of solid citric acid
9. customto give a very dark brown-orange solution
10. customThe organic layer was separated
11. washwashed with water, saturated NaHSO3, brine
12. dry with materialdried over MgSO4
13. customevaporated
14. customto provide 9.5 g (96%) of title acid as a brown-yellow solid which
15. customwas used directly in the following reaction

ORD record

ord-03ff0a7322d94ded8537c865e73ad7be

Source dataset

uspto-grants-1994_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05278153