Formic Acid → HCID 59536838, compound

Temperature

0 °C

A quantity of 171 μl (1.97 mmol) of chlorosulphonyl isocyanate was admixed under argon at 0° C., with vigorous stirring, with 74 μl (1.97 mmol) of anhydrous formic acid. Following the addition, the reaction mixture solidified within seconds. A quantity of 2 ml of dichloromethane was added. The reaction mixture was then stirred further at 0° C. for 1 h and then RT for 8 h. Thereafter it was cooled to 0° C. again and admixed with a solution of 400 mg (1.31 mmol) of the compound from Example 59A and 159 μl (1.97 mmol) of pyridine in 2 ml of dichloromethane. The cooling bath was removed and the reaction mixture was stirred overnight at RT. For work-up, 5 ml of water and 5 ml of ethyl acetate were added. After 10 min, the mixture was diluted with 100 ml of ethyl acetate, and washed twice with water and once with saturated aqueous sodium chloride solution. The organic phase was dried over sodium sulphate and freed from the solvent on a rotary evaporator. The residue was purified by preparative HPLC [Method 10]. The product fraction was freed from the solvent on a rotary evaporator. Drying in an HV gave 260 mg (52% of theory) of the title compound.

1. additionthe addition
2. waitthe reaction mixture solidified within seconds
3. waitRT for 8 h
4. temperatureThereafter it was cooled to 0° C. again
5. customThe cooling bath was removed
6. stirringthe reaction mixture was stirred overnight at RT
7. additionFor work-up, 5 ml of water and 5 ml of ethyl acetate were added
8. waitAfter 10 min
9. additionthe mixture was diluted with 100 ml of ethyl acetate
10. washwashed twice with water and once with saturated aqueous sodium chloride solution
11. dry with materialThe organic phase was dried over sodium sulphate
12. customfreed from the solvent on a rotary evaporator
13. customThe residue was purified by preparative HPLC [Method 10]
14. customThe product fraction was freed from the solvent on a rotary evaporator
15. customDrying in an HV

ORD record

ord-9490e093c8d74177b004059337edaa02

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796324B2