Isopropyl chloroformate → Isopropyl 5-(2-hydroxyethyl)thiophene-2-carboxylate

A solution of n-butyllithium (37 mL of a 1.6 M solution in hexanes, 59.2 mmol) was added slowly to a solution of tert-butyldimethyl(2-(thiophen-2-yl)ethoxy)silane (see U.S. Pat. No. 5,739,141; 9.5 g, 39.0 mmol) in THF (100 mL) at −78° C. After 1 h at −78° C., isopropyl chloroformate (60 mL of a 1.0 M solution in toluene, 60 mmol) was added slowly. After 1 h at −78° C., the reaction was quenched by addition of saturated aqueous NH4Cl (150 mL) and was allowed to warm to room temperature. The phases were separated and the organic phase was dried (Na2SO4), filtered (washing with excess THF) and concentrated in vacuo. The crude residue was dissolved in THF (100 mL), cooled to 0° C. and treated with tetrabutylammonium fluoride (43 mL of a 1.0 M solution in THF, 43 mmol). The reaction was allowed to warm to room temperature and was stirred overnight. The reaction was concentrated in vacuo, saturated aqueous NH4Cl (100 mL) was added and the mixture was extracted with EtOAc (3×150 mL). The combined extracts were washed with brine (100 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified on 330 g silica (40% EtOAc/hexanes→60% EtOAc/hexanes, gradient) to afford 6.6 g (71%) of isopropyl 5-(2-hydroxyethyl)thiophene-2-carboxylate.

1. customat −78° C
2. waitAfter 1 h at −78° C.
3. customthe reaction was quenched by addition of saturated aqueous NH4Cl (150 mL)
4. customThe phases were separated
5. dry with materialthe organic phase was dried (Na2SO4)
6. filtrationfiltered
7. wash(washing with excess THF)
8. concentrationconcentrated in vacuo
9. dissolutionThe crude residue was dissolved in THF (100 mL)
10. temperaturecooled to 0° C.
11. additiontreated with tetrabutylammonium fluoride (43 mL of a 1.0 M solution in THF, 43 mmol)
12. temperatureto warm to room temperature
13. concentrationThe reaction was concentrated in vacuo, saturated aqueous NH4Cl (100 mL)
14. additionwas added
15. extractionthe mixture was extracted with EtOAc (3×150 mL)
16. washThe combined extracts were washed with brine (100 mL)
17. dry with materialdried (Na2SO4)
18. filtrationfiltered
19. concentrationconcentrated in vacuo
20. customThe crude residue was purified on 330 g silica (40% EtOAc/hexanes→60% EtOAc/hexanes, gradient)

ORD record

ord-4f8c241b13ef4a849966469016a2f1cb

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090584B2