Hydrochloric Acid → Ethyl 2-[(2-hydroxy-4-{[5-(methylsulfonyl)pyridin-2-yl]oxy}phenyl)hydrazono]propanoate

HRID 1188919Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][N:10]=2)=[CH:4][C:3]=1[OH:19].Cl.[N:21]([O-])=O.[Na+].[CH3:25][CH:26](C(=O)C)[C:27]([O:29][CH2:30][CH3:31])=[O:28].[OH-].[K+]>C(O)C.C(#N)C.O.C(OCC)(=O)C>[OH:19][C:3]1[CH:4]=[C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][N:10]=2)[CH:6]=[CH:7][C:2]=1[NH:1][N:21]=[C:26]([CH3:25])[C:27]([O:29][CH2:30][CH3:31])=[O:28]

Participants

Conditions

Temperature: -5 °C

Procedure

To a stirring suspension of 2-amino-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}phenol (27.68 g) in a mixture of ethanol (150 mL) and acetonitrile (20 mL) was added concentrated hydrochloric acid (21.8 mL) at 0° C. After cooling to −5° C., a solution of sodium nitrite (8.18 g) in water (20 mL) was added dropwise to the mixture with keeping the temperature below −5° C. The mixture was stirred at −10° C. for 30 min. The mixture was added to a mixture of ethyl 2-methyl-3-oxobutanoate (15.7 mL), potassium hydroxide (85%, 22.8 g), ethanol (50 mL) and water (150 mL) at −30 to −20° C. After stirring at −30° C. for 1 h, 1M hydrochloric acid (150 mL) was added to the mixture. Water and ethyl acetate were added. The resulting brown suspension was filtered to give the title compound (17.9 g) as a brown solid. Furthermore, the filtrate was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residual solid was washed with diethyl ether to give the title compound (15.3 g) as a brownish solid. Additionally, the filtrate was concentrated and the residual solid was washed with diethyl ether to give the title compound (4.5 g) as a brownish solid (total 37.7 g, 97%). MS 394 (MH+).

Workup

customthe temperature below −5° C
stirringAfter stirring at −30° C. for 1 h
filtrationThe resulting brown suspension was filtered

Sources & evidence

ORD record: ord-d7a244ecd3824b19951d0e346804f0c3
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673942B2

Reaction notes

Loading…