Penicillin V potassium salt synthesis

Yield:132-98-9 80%

Reaction Conditions:

Stage #1:6-Aminopenicillanic Acid;Phenoxyacetyl chloride with sodium hydrogencarbonate in water;acetone at 10 - 15; for 0.333333 h;
Stage #2: with potassium 2-ethylhexanoate in butan-1-ol

Steps:

1 2.1 Procedure for synthesis of intermediate penicillin V
To a cooled and stirred solution of 2.76 g (12.5 mmol) of 6-APA in 60 mL of water containing 5.25 g (62.5 mmol) of sodium bicarbonate, a solution of 2.76 g (16.2 mmol) phenoxyacetyl chloride in 5 mL of acetone was added in one minute. The resulting mixture was stirred vigorously during 20 min while the temperature was kept at 10-15 °C. The clear solution was extracted twice with 15 mL portions of methyl isobutyl ketone (MIBK). The clear aqueous solution was cooled to 5-10 °C and acidified to pH 2 with a cold 5.0 mol/L sulfuric acid solution. The acidified aqueous solution was extracted with 50 mL MIBK twice. The MIBK extract was separated, washed with cold water, and dried for 10 min over anhydrous sodium sulfate. After filtration, 10 mL of a 25% solution of potassium 2-ethylhexanoate in butanol was added. The white crystalline material was collected by filtration, washed on the filter with dry acetone and dried in vacuum, yield 3.5 g (80%) penicillin V as a white solid. Mp: 210-211 °C (dec.). ¹H NMR (400 MHz, DMSO-d₆): δ 8.42 (d, 1H, J = 8.0 Hz), 7.27 (m, 2H), 6.92 (m, 3H), 5.42 (dd, 1H, J = 8.0 Hz, 4.0 Hz), 5.40 (d, 1H, J = 4.0 Hz), 4.62 (d, 2H, J = 2.2 Hz), 3.88 (s, 1H), 1.52 (s, 3H), 1.46 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆): δ 172.8, 169.0, 168.1, 158.1, 130.0, 121.7, 115.0, 74.6, 67.3, 66.7, 65.0, 57.8, 32.7, 27.8; HRMS (FAB) calcd. for C₁₆H₁₈KN₂O₅S [M+H]⁺: m/z 389.0584; found: 389.0995.

References:

Liu, Chun-Jing;Dutta, Dinah;Mitscher, Lester [Chinese Chemical Letters,2015,vol. 26,# 1,p. 113 - 117]

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