Acetone → HCID 68747463, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (S)—N-(2-(biphenyl-4-yl)-1-(1-methyl-1H-tetrazol-5-yl)ethyl)-1-(2-chloroallyl)cyclopentanecarboxamide and (S)—N-(2-(biphenyl-4-yl)-1-(2-methyl-2H-tetrazol-5-yl)ethyl)-1-(2-chloroallyl)cyclopentanecarboxamide in acetone at −7° C. was bubbled ozone for 30 seconds using ozone generator. The mixture became a persistent pale blue color. The mixture was stirred at −78° C. for 1 minute. To the mixture was bubbled oxygen gas for 10 minutes and was added dimethyl sulfide (0.5 mL) followed by water (1 mL). The cooling bath was removed and stirred for 1 hour at room temperature. The mixture was concentrated under reduced pressure and diluted in EtOAc. The mixture was acidified with 1 M HCl until pH=1. The organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated under reduced pressure. The obtained residue was purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN gradient) to give two isomers, (S)-2-(1-(2-(biphenyl-4-yl)-1-(1-methyl-1H-tetrazol-5-yl)ethylcarbamoyl)cyclopentyl)acetic acid and (S)-2-(1-(2-(biphenyl-4-yl)-1-(2-methyl-2H-tetrazol-5-yl)ethylcarbamoyl)cyclopentyl)acetic acid (11 mg, regioisomer 1, 7.6 mg regioisomer 2). Regioisomer 1: HPLC retention time=1.57 minutes (condition D); MS (m+1)=434.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.57-1.85 (m, 6H), 1.89-2.19 (m, 2H), 2.73 (q, J=16.4 Hz, 2H), 3.18-3.41 (m, 1H), 3.48 (dd, J=13.3, 6.4 Hz, 1H), 3.69 (s, 3H), 5.42-5.65 (m, 1H), 7.03 (br. s., 1H), 7.08-7.24 (m, 2H), 7.34-7.41 (m, 1H), 7.42-7.65 (m, 6H). Regioisomer 2: HPLC retention time=1.66 minutes (condition D); MS (m+1)=434.3. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44-1.73 (m, 6H), 1.73-1.99 (m, 2H), 2.59 (s, 2H), 3.15-3.38 (m, 2H), 4.24 (s, 3H), 5.50-5.79 (m, 1H), 6.60 (br. s., 1H), 7.06 (d, J=8.1 Hz, 2H), 7.19 (s, 2H), 7.22-7.30 (m, 1H), 7.30-7.56 (m, 4H).

Provenance & Evidence