Water → 3-(5-{(1R)-1-[5-(3-chlorophenyl)isoxazol-3-yl] ethoxy}-4-methyl-4H-1,2,4-triazol-3-yl)pyridine

HRID 1453808Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][N:11]=[C:10]([C@H:13]([OH:15])[CH3:14])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:16][N:17]1[C:21](S(C)(=O)=O)=[N:20][N:19]=[C:18]1[C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][N:11]=[C:10]([C@H:13]([O:15][C:21]3[N:17]([CH3:16])[C:18]([C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)=[N:19][N:20]=3)[CH3:14])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

(1R)-1-[5-(3-chlorophenyl)isoxazol-3-yl]ethanol (5.40 g, 24.1 mmol) was dissolved in DMF (45 mL). To this 3-[4-methyl-5-(methylsulfonyl)-4H-1,2,4-triazol-3-yl]pyridine (5.75 g, 24.1 mmol) and cesium carbonate (10.1 g, 31.4 mmol) were added. After stirring over night at 60° C., water was added. The mixture was extracted with dichloromethane, followed by concentration of the organic layer in vacuo, to give a crude which was purified by column chromatography on silica using dichloromethane/methanol=98/2, to give the title compound (7.10 g, 77%). 1H NMR: 8.90 (d, 1H), 8.72 (m, 1H), 8.04 (dt, 1H), 7.76 (bs, 1H), 7.66 (m, 1H), 7.45 (m, 1H), 7.40 (m, 2H), 6.73 (s, 1H), 6.35 (q, 1H), 3.57 (s, 3H), 1.93 (d, 3H). 1H NMR (DMSO-d6): 8.90 (d, 1H), 8.71 (dd, 1H), 8.13 (dt, 1H), 7.99 (s, 1H), 7.86 (m, 1H), 7.58 (m, 3H), 7.40 (s, 1H), 6.19 (q, 1H), 3.54 (s, 3H), 1.81 (d, 3H). LC-MS (M++1)=382. [α]DRT (2.92 g/L, CDCl3)=−46.575°

Workup

extractionThe mixture was extracted with dichloromethane
customto give a crude which
customwas purified by column chromatography on silica

Sources & evidence

ORD record: ord-119cdbdd3f3a43b4aed412769541108a
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07476684B2

Reaction notes

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