Pyridine → HCID 52933643, compound

To a solution of 1-methylethyl {(2S,4R)-1-acetyl-6-[(hydroxyamino)(imino)methyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (for a preparation, see Intermediate 56) (130 mg, 0.373 mmol) in toluene (2 mL) and pyridine (2 mL) was added acetyl chloride (a solution 0.34 mL of acetyl chloride in 5 mL of toluene was made and 0.52 mL was used, 0.485 mmol) dropwise and the resulting mixture was stirred at room temperature under nitrogen for 30 min. The mixture was then warmed to 110° C. and stirred at this temperature for 16 h then cooled to room temperature. Most of the solvents were removed in vacuo and the residue was partitioned between AcOEt and water (acidified to pH 1 with a 2N HCl aqueous solution). The two layers were separated and the aqueous phase was extracted with AcOEt. The combined organic phases were washed with a saturated NaHCO3 aqueous solution then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient: 13 to 63% AcOEt in hexanes) gave 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(5-methyl-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (120 mg, 0.322 mmol, 86% yield) as a white foam. LCMS (method A): Retention time 0.94 min, [M+H]+=373.05

1. temperatureThe mixture was then warmed to 110° C.
2. stirringstirred at this temperature for 16 h
3. temperaturethen cooled to room temperature
4. customMost of the solvents were removed in vacuo
5. customthe residue was partitioned between AcOEt and water (
6. customThe two layers were separated
7. extractionthe aqueous phase was extracted with AcOEt
8. washThe combined organic phases were washed with a saturated NaHCO3 aqueous solution
9. dry with materialbrine, dried over MgSO4
10. concentrationconcentrated in vacuo
11. customPurification of the residue on SP4

ORD record

ord-f0fea7fbc4a24a36846ab5d9b791aaf9

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697725B2