Formic Acid → N-(2,4-dimethylphenyl)-4-(1-hydroxy-2-(2H-tetrazol-5-yl)ethyl)-N-isobutylbenzenesulfonamide

Temperature

-78 °C

To a solution of 5-methyl-2-trityl-2H-tetrazole (68.5 mg, 0.21 mmol) in tetrahydrofuran (THF) (1 mL), stirred under nitrogen at −70° C., was added a solution of n-BuLi (1.6 M in hexanes, 0.144 mL, 0.231 mmol) and tetrahydrofuran (THF) (1 mL) dropwise over 1 minute. The reaction mixture was stirred at −78° C. for 45 minutes. N-(2,4-dimethylphenyl)-4-formyl-N-isobutylbenzenesulfonamide (222 mg, 0.643 mmol) in tetrahydrofuran (THF) (1 mL) was then added dropwise at −78° C. over 1 minute. The reaction mixture was stirred at −78° C. for 2 hours, then allowed to warm to room temperature. The reaction was carefully quenched using a few drops of water under nitrogen. Ethyl acetate (3 mL) and water (2 mL) were added and the reaction stirred vigorously for 5 minutes. The organic phase was separated (hydrophilic frit) then evaporated in vacuo to give a residue. The residue was redissolved in dichloromethane (DCM) (2 mL) and treated with formic acid (0.5 mL, 13.04 mmol). The solution was stood overnight, then the solvent evaporated in vacuo and the crude purified by MDAP (Method F) to give the required product, 17.3 mg. LCMS (M+1) 430, RT 1.09 mins.

1. stirringThe reaction mixture was stirred at −78° C. for 2 hours
2. temperatureto warm to room temperature
3. customThe reaction was carefully quenched
4. additionEthyl acetate (3 mL) and water (2 mL) were added
5. stirringthe reaction stirred vigorously for 5 minutes
6. customThe organic phase was separated (hydrophilic frit)
7. customthen evaporated in vacuo
8. customto give a residue
9. waitThe solution was stood overnight
10. customthe solvent evaporated in vacuo
11. customthe crude purified by MDAP (Method F)

ORD record

ord-e6f8a5aaf27b4c188c66c0beda3b6c77

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150508B2