Hydrochloric Acid → N-[(1R)-1-(5-hydroxypyridine-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide

HRID 2383527

Reaction equation

[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22]C)=[CH:18][N:17]=2)[CH3:15])=[O:12])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[C-]#N.[Na+].Cl>CS(C)=O.C(Cl)Cl.O>[OH:22][C:19]1[CH:20]=[CH:21][C:16]([C@H:14]([NH:13][C:11](=[O:12])[CH2:10][C:7]2[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=2)[CH3:15])=[N:17][CH:18]=1

Participants

Conditions

Temperature: 175 °C

Procedure

2-(4-Isopropylphenyl)-N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]acetamide (3.8 g, 12.2 mmol) (Example 11) was dissolved in DMSO (20 mL) and transferred to a sealed tube. To this solution was added NaCN (3.6 g, 73.0 mmol) and the mixture was stirred at 175° C. for 16 h. The mixture was cooled to room temperature and diluted with CH2Cl2 (200 mL) and water (100 mL). The pH of the aqueous layer was brought to neutral by the addition of 2N HCl and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL), concentrated, and purified by normal phase chromatography (2-10% MeOH/CH2Cl2) to give N-[(1R)-1-(5-hydroxypyridine-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide as a tan solid. 1H NMR (CDCl3, 400 MHz) δ 8.06 (t, J=1.65 Hz, 1H), 7.17 (m, 4H), 7.02 (m, 2H), 6.67 (d, J=7.50 Hz, 1H), 5.03 (quint., J=6.96 Hz, 1H), 3.53 (d, J=2.20 Hz, 2H), 2.88 (sept., J=6.69 Hz, 1H), 1.38 (d, J=6.77 Hz, 3H), 1.23 (d, J=6.95, 6H); MS (Electrospray): m/z 299.3 (M+H).

Workup

customtransferred to a sealed tube
temperatureThe mixture was cooled to room temperature
customthe layers were separated
washThe organic layer was washed with water (100 mL) and brine (100 mL)
concentrationconcentrated
custompurified by normal phase chromatography (2-10% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-8e81865dcf264317a176bade9c5753d4
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08263627B2

Linked notes

Loading…