Diethyl Oxalate → Ethyl 4-(hydroxyimino)-3-methyl-2-oxo-4-(thiophen-2-yl)butanoate

1-(Thiophen-2-yl)propan-1-one oxime (6.3 g, 40.6 mmol) was dissolved in 100 mL of THF and cooled to 0° C. LDA solution (46.7 mL, 93.5 mmol, 2M in heptane/THF/ethyl benzene) was added dropwise, and the reaction mixture was stirred at 0° C. for 1 hour and then warmed to room temperature. The mixture was then transferred to an addition funnel and added dropwise to a flask containing a pre-cooled mixture of diethyl oxalate (27.6 mL, 203 mmol) and THF (100 mL) at 0° C. After the addition was complete, the reaction mixture was stirred at room temperature for 18 hours. The mixture was cooled in an ice bath and quenched with 150 mL of 10% hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with EtOAc. The aqueous layer was then neutralized with solid sodium bicarbonate and extracted further with CH2Cl2. The organic layers were combined, dried over MgSO4 and concentrated. The crude oil was purified by chromatography (0-20% EtOAc/hexanes) to give 7.7 g of the title compound. MS: (+) m/z 256.33 (M+1).

1. temperaturewarmed to room temperature
2. customThe mixture was then transferred to an addition funnel
3. additionadded dropwise to a flask
4. additioncontaining
5. additionAfter the addition
6. stirringthe reaction mixture was stirred at room temperature for 18 hours
7. temperatureThe mixture was cooled in an ice bath
8. customquenched with 150 mL of 10% hydrochloric acid
9. customThe organic layer was separated
10. extractionthe aqueous layer was extracted with EtOAc
11. extractionextracted further with CH2Cl2
12. dry with materialdried over MgSO4
13. concentrationconcentrated
14. customThe crude oil was purified by chromatography (0-20% EtOAc/hexanes)

ORD-Eintrag

ord-d014612d168247018b0ea0fe3c5a88a8

Quelldatensatz

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08269008B2