Bis(2-pyridyl) ketone → (Z)-2-Heptenoic acid

Temperature

0 °C

To a cooled (0° C.) solution of 293.6 mg (0.74 mmol) of the pyridyl ketone and 670.4 mg (1.48 mmol) of (5-carboxypentyl)-triphenylphosphonium bromide in 2.5 mL of THF was added dropwise 2.95 mL (2.95 mmol) of 1.0 M t-BuOK in THF over 10 min period. The dark brown solution was stirred at 0° C. for 1.5 h, and then the reaction was quenched with 20 mL of saturated aqueous NH4Cl. The mixture was extracted with 3× 50 ML of CH2Cl2. The combined extract was dried over MgSO4, concentrated and purified by preparative HPLC with MeOH--AcOH--CH2Cl2 (2:1:97) as the eluent to afford 56.1 mg (8.4%) of the less polar (Z)-heptenoic acid and 434.9 mg of the (E)-isomer containing a byproduct from the Wittig salt. In order to purify it, the (E)-isomer was therefore esterified with CH2N2 which was generated by a standard method from MNNG and aqueous NaOH in Et2O. The ester was isolated cleanly by flash chromatography with EtOAc-hexanes-CH2Cl2 (2:1:1) as the eluent. The ester (102.5 mg) was then hydrolyzed with 1 N NaOH in THF--MeOH (1:1). Flash chromatography with EtOAc--MeOH--AcOH--CH2Cl2 (50:1:1:48) yielded 92.5 mg (25%) of the pure (E)-heptenoic acid: mp 56-61° C.; 1H NMR (CDCl3) δ8.58 (s, 1H), 8.47 (d, J=4.1 Hz, 1H), 8.26 (s, 1H), 8.02 (d, J=8.2 Hz, 2H), 7.44 (dt, J=8.0, 1.5 Hz, 1H), 7.35-7.16 (m, 9H), 6.19 (t, J=7.4 Hz, 1H), 3.70 (dt, J=6.9, 6.7 Hz, 2H), 2.94 (t, J=7.2 Hz, 2H), 2.32 (t, J=7.8 Hz, 2H), 2.20 (ddd, J=7.3, 7.2, 7.0 Hz, 2H), 1.68-1.51 (m, 4H); FDMS 496 (M+1). Anal. (C30H29N3O4.0.1C2H4O2) C, H, N.

1. customthe reaction was quenched with 20 mL of saturated aqueous NH4Cl
2. extractionThe mixture was extracted with 3× 50 ML of CH2Cl2
3. extractionThe combined extract
4. dry with materialwas dried over MgSO4
5. concentrationconcentrated
6. custompurified by preparative HPLC with MeOH

ORD record

ord-7e883af5e0f74a1a9ea54ca7462c70e5

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05990308