Diethyl Ether → 3-Bromothiophene-2-carboxylic acid

To a solution of 3-bromothiophene (600.0 g, 3.68 mol) in THF (3 L) cooled to −72° C. was added LDA (1.93 L, 3.86 mol, 2 N) slowly over 2 hours. The rate of LDA addition is such that the reaction temperature never exceeded 48° C. After complete addition, the solution is stirred for an additional 40 minutes. Diethyl ether (3 L) is then added via an addition funnel such that the temperature is maintained below −65° C. The addition funnel is then replaced with a dispersion tube and CO2 gas is bubbled through the solution for 3 hours. Dry ice (500 g) is then added and the mixture is stirred overnight. The reaction flask is then placed in an ice bath and 6 N HCl is added slowly to prevent excessive bubbling until the pH of the solution is adjusted to 1-2. The resulting mixture is then extracted with EtOAc. The extract is washed with brine then dried over MgSO4, filtered and evaporated. The product is dried under vacuum at room temperature yielding 585.15 g (77%) as an off-white solid.

1. customis such that the reaction temperature never exceeded 48° C
2. additionAfter complete addition
3. temperatureis maintained below −65° C
4. customThe addition funnel is then replaced with a dispersion tube
5. customCO2 gas is bubbled through the solution for 3 hours
6. additionDry ice (500 g) is then added
7. stirringthe mixture is stirred overnight
8. customThe reaction flask is then placed in an ice bath
9. addition6 N HCl is added slowly
10. customto prevent excessive bubbling until the pH of the solution
11. extractionThe resulting mixture is then extracted with EtOAc
12. washThe extract is washed with brine
13. dry with materialthen dried over MgSO4
14. filtrationfiltered
15. customevaporated
16. customThe product is dried under vacuum at room temperature
17. customyielding 585.15 g (77%) as an off-white solid

ORDレコード

ord-55cf057d3a46401e8242bc3dc939dfdf

出典データセット

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07772252B2