Methyl 5-formyl-1-(1-methylethyl)-1H-pyrazole-3-carboxylate → HCID 89370561, Verbindung

Temperatur

-78 °C

A suspension of methyltriphenylphosphonium bromide (2.69 g, 7.52 mmol) in dry THF (40 mL) was cooled to −78° C. and n-butyllithium (1.6 M solution in hexane, 3.7 mL, 5.91 mmol) was added dropwise. The yellow-orange suspension was stirred at −78° C. for 50 min and then a solution of methyl 5-formyl-1-isopropyl-1H-pyrazole-3-carboxylate (prepared as described in WO 2011/020615, 1.05 g, 5.37 mmol) in dry THF (10 mL) was added dropwise. The mixture was stirred at −78° C. for 1.75 h, the cooling bath was removed and the mixture (off-white suspension) was stirred at rt for 1 h. The mixture was then partitioned between diluted aq. NaHCO3 solution (150 mL) and EA (150 mL). The aq. layer was extracted twice with EA (50 mL each) and the combined organic layer was washed twice with water (50 mL each) and concentrated without drying to give 2.74 g of a yellow oil which slowly crystallized. The crude product was purified by CC (preadsorption with CH2Cl2, hexane/EA 4:1) to give alkene 7a (590 mg, 57%) as a colorless oil. 1H NMR (DMSO-d6) δ: 7.02 (s, 1H), 6.87 (dd, J=17.3, 11.2 Hz, 1H), 5.94 (dd, J=17.3, 1.3 Hz, 1H), 5.45 (dd, J=11.2, 1.3 Hz, 1H), 4.80 (sept, J=6.6 Hz, 1H), 3.79 (s, 3H), 1.38 (d, J=6.6 Hz, 6H). C10H14N2O2 (194.23). LC-MS (ESI): 195 [M+H]+.

1. stirringThe mixture was stirred at −78° C. for 1.75 h
2. customthe cooling bath was removed
3. stirringthe mixture (off-white suspension) was stirred at rt for 1 h
4. customThe mixture was then partitioned between diluted aq. NaHCO3 solution (150 mL) and EA (150 mL)
5. extractionThe aq. layer was extracted twice with EA (50 mL each)
6. washthe combined organic layer was washed twice with water (50 mL each)
7. concentrationconcentrated
8. customwithout drying

ORD-Eintrag

ord-0d79606338454adfa8d0ce8ff2e86304

Quelldatensatz

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09139539B2