5-(4-BROMOPHENYL)-5-OXOVALERIC ACID

A flask was charged with AlCl3 (78.8 mmol, 10.5 g, 2.3 equiv) and dry CH2Cl2 (25 ml) under calcium chloride guard tube and the formed suspension was stirred on ice bath. Subsequently, a solution of glutaric anhydride 10 (34.3 mmol, 3.91 g) in dry CH2Cl2 (15 ml) was added dropwise (t < 7 °C). The resulting mixture was stirred on ice bath for 30 minutes and bromobenzene 11b (34.3 mmol, 5.39 g, 1.0 equiv) was carefully added afterwards. The cooling bath was removed and the mixture was stirred at room temperature for 19 hours, then it was poured into ice water (15 ml), acidified with conc. H2SO4 (10 ml), the aqueous layer was extracted with ethyl acetate (1 x 100 ml, 2 x 50 ml), the combined organics were dried over Na2SO4, filtered and concentrated. The crude product was dissolved in ethyl acetate and the resulting solution was added dropwise to a vigorously stirred cold hexanes (1 L). The precipitate was filtered off and dried to provide 5-(4-bromophenyl)-5-oxopentanoic acid (7.93 g, 85percent) as a yellow powder;2 mp 125-127 °C; 1H NMR (300 MHz, CDCl3): δ = 2.07 (m, 2H), 2.50 (t, J = 7.2 Hz, 2H), 3.04 (t, J = 7.2 Hz, 2H), 7.60 (m, 2H), 7.82 (m, 2H). 5-(4-Bromophenyl)-5-oxopentanoic acid (25.0 mmol, 6.78 g), paraformaldehyde (86.3 mmol, 2.59 g, 3.4 equiv) and piperidine (0.57 ml, 0.24 equiv) were dissolved/suspended in pyridine (42 ml) and stirred at 70 °C for 21 hours. Afterwards, the mixture was poured into 1M H2SO4 (200 ml)/conc. H2SO4 (15 ml), the aqueous layer was extracted with ethyl acetate (1 x 150 ml, 2 x 100 ml), the combined organics were washed with half-saturated brine (300 ml), dried over Na2SO4, filtered and concentrated. The crude product was crystallized from ethyl acetate to yield 4-(4-bromobenzoyl)pent-4-enoic acid 9b (3.93 g, 56percent) as an orange-yellow solid; mp 127-128 °C; 1H NMR (300 MHz, CDCl3): δ = 2.63 (t, J = 6.9 Hz, 2H), 2.80 (t, J = 6.9 Hz, 2H), 5.67 (s, 1H), 5.95 (s, 1H), 7.60 (m, 4H); 13C NMR (75 MHz, CDCl3): δ = 27.2, 32.6, 127.3, 127.4, 131.0, 131.6, 136.3, 145.8, 178.9, 196.6.

Molecular Weight:271.11
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:5
Exact Mass:269.98916
Monoisotopic Mass:269.98916
Topological Polar Surface Area:54.4
Heavy Atom Count:15
Complexity:232
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes