1-Piperidinecarboxaldehyde → 3-hexylthiophene-2-carbaldehyde

Temperature

-40 °C

To the solution of 2-bromo-3-hexylthiophene (13.5 g, 54.6 mmol) in anhydrous tetrahydrofuran (200 mL) in a dry ice/acetone bath at −78° C. was added n-butyl lithium (2.5 M in hexane, 24.0 mL, 60.1 mmol) dropwise under the protection of argon. The reaction solution was warmed to −40° C. and stirred for 60 min. The solution was cooled down to −78° C. again, and 1-formylpiperidine (7.41 g, 65.5 mmol) was added in one shot. Then, the solution was allowed to warm slowly up to room temperature and stirred overnight. The solution was then poured into ice water. The organic layer was separated and the aqueous layer was extracted twice with hexane (100 mL). The organic extracts were combined and washed three times with distilled water (50 mL), dried over anhydrous magnesium sulfate, and rotary evaporated to remove the solvent. The liquid residue was subjected to silica-gel column chromatography (EtOAc/hexane=1/10, Rf=0.4) to yield a clear liquid product (9.8 g, 92% yield). 1H NMR (400 MHz, acetone-d6) δ (ppm): 10.11 (s, 1H); 7.89 (d, 1H, J=5.2 Hz); 7.17 (d, 1H, J=5.2 Hz); 3.04 (t, 2H, J=7.8 Hz); 1.69 (m, 2H); 1.28-1.42 (m, 6 H); 0.87 (m, 3H).

1. temperatureThe solution was cooled down to −78° C. again
2. temperatureto warm slowly up to room temperature
3. stirringstirred overnight
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted twice with hexane (100 mL)
6. washwashed three times with distilled water (50 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. customrotary evaporated
9. customto remove the solvent

ORD record

ord-5a854095c4424a8598e2339e2e0b3a0f

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673183B2