Sodium Cyanide → 2-(1,1'-biphenyl-4-yl)-N-[(1R)-1-(5-hydroxypyridin-2-yl)ethyl]acetamide

HRID 2383523Notes

Reaction equation

[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([CH2:7][C:8]([NH:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][N:14]=2)[CH3:12])=[O:9])=[CH:3][CH:2]=1.[C-]#N.[Na+]>CS(C)=O>[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:2]=[CH:3][C:4]([CH2:7][C:8]([NH:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][N:14]=2)[CH3:12])=[O:9])=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 180 °C

Procedure

To a mixture of 2-(1,1′-biphenyl-4-yl)-N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]acetamide (200 mg, 0.58 mmol) in DMSO (4.0 ml) was added sodium cyanide (141 mg, 2.89 mmol) and heated to 180° C. for one hour. An additional amount of sodium cyanide (207 mg, 4.22 mmol) was added and the mixture was further heated for another hour until no significant increase in desired product was observed by LC/MS. After cooling reaction to room temperature, the reaction was taken to neutral pH with the careful addition of 1.0 N HCl solution. Organics were extracted with EtOAc, dried over Na2SO4, filtered and concentrated in vacuo to give an oil. Normal phase chromatography (0-100% EtOAc/Hex) afforded 2-(1,1′-biphenyl-4-yl)-N-[(1R)-1-(5-hydroxypyridin-2-yl)ethyl]acetamide as an oil. 1H NMR (CDCl3, 400 MHz) δ 9.55 (brs, 1H); 8.07 (m, 1H); 7.50 (m, 4H); 7.41 (m, 2H); 7.28 (m, 3H); 7.00 (m, 2H); 6.82 (d, J=7.20 Hz, 1H); 5.03 (m, 1H); 3.57 (s, 2H); 1.37 (d, J=6.40 Hz, 3H); MS (Electrospray): m/z 333.1 (M+H).

Workup

temperaturethe mixture was further heated for another hour until

Sources & evidence

ORD record: ord-8a167af7a0e543e8a711a2d9134cd84c
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08263627B2

Reaction notes

Loading…