Ammonium Acetate → HCID 67751390, compound

A 13% solution of titanium trichloride in 20% hydrochloric acid (143 ml) was added to a degassed solution of ammonium acetate (56 g) in water (200 ml) at 0° C. under nitrogen over 30 min. A solution of potassium t-butoxide (1.91 g) in methanol (40 ml) was added to a solution of 4-nitro-2-oxo-5-pyridylpiperidine (3.01 g, Example 26a) in methanol (65 ml) and the mixture was stirred for 15 min. This solution was then added dropwise to the titanium trichloride/buffer solution at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 15 min. Methanol was removed in vacuo and solid sodium hydroxide was added, with stirring and cooling, to the residual solution. The mixture was filtered and water was removed from the filtrate in vacuo. The residue was azeotroped with toluene and then redissolved in dichloromethane. Insoluble material was filtered off and the filtrate was concentrated in vacuo. The material was freeze-dried for 18 h to give 5-hydroxy-2-oxo-6-pyridylpiperidine as a mixture of cis and trans isomers. 1H NMR (250 MHz, CDCl3) δ1.91-2.18 (2H, m, CH2), 2.39-2.57 (1H, m, CHH), 2.60-2.84 (1H, m, CHH), 4.02-4.11 (0.4H, CHOH, trans isomer), 4.37-4.44 (0.6H, m, CHOH, cis isomer), 4.61 (0.4H, brd, NCH, trans isomer), 4.69 (0.6H, brd, NCH, cis isomer), 7.30-7.50 (2H, m, ArH), 7.77-7.88 (1H, m, ArH), 8.54-8.64 (1H, m, ArH).

1. stirringThe reaction mixture was stirred at 0° C. for 15 min
2. customMethanol was removed in vacuo and solid sodium hydroxide
3. additionwas added
4. stirringwith stirring
5. temperaturecooling, to the residual solution
6. filtrationThe mixture was filtered
7. customwater was removed from the filtrate in vacuo
8. customThe residue was azeotroped with toluene
9. dissolutionredissolved in dichloromethane
10. filtrationInsoluble material was filtered off
11. concentrationthe filtrate was concentrated in vacuo
12. customThe material was freeze-dried for 18 h

ORD record

ord-8a23391e4d6e4029a6ab37bfe50ecf1f

Source dataset

uspto-grants-1995_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05459270