Sodium Hydroxide → HCID 178503116, compound

HRID 423648Notes

Reaction equation

N([O-])=O.[Na+].[F:5][C:6]1[CH:11]=[C:10]([S:12][CH3:13])[CH:9]=[CH:8][C:7]=1[C:14]1[N:15]=[CH:16][C:17](N)=[N:18][CH:19]=1.[OH-:21].[Na+]>S(=O)(=O)(O)O.CCO>[F:5][C:6]1[CH:11]=[C:10]([S:12][CH3:13])[CH:9]=[CH:8][C:7]=1[C:14]1[N:15]=[CH:16][C:17]([OH:21])=[N:18][CH:19]=1

Participants

Conditions

Temperature: 45 °C

Procedure

Sodium nitrite (1.73 g, 25.1 mmol) was added portionwise to concentrated sulfuric acid (20 mL) at 0° C. The mixture was stirred at 45° C. until homogeneous, cooled to 0° C., and charged with a solution of 5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinamine (4.37 g, 18.6 mmol) in concentrated sulfuric acid (55 mL) at 0° C. The reaction was allowed to warm to 25° C., stirred for 15 min, then at 45° C. for 1 h. The reaction was poured onto ice and the pH was adjusted to ˜4 with 10N NaOH. The resulting tan precipitate was filtered, washed with water, and air-dried to afford a tan solid. The solid was refluxed in EtOH (300 mL), hot-filtered, and the filtrate concentrated to afford 5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinol (and tautomers thereof) (3.16 g, 72% yield, purity=87%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ8.14 (d, 1H, J=1.2 Hz), 7.72-7.86 (m, 2H), 7.24-7.15 (m, 2H), 2.52 (s LRMS (ESI), m/z 237 (M+H).

Workup

temperaturecooled to 0° C.
temperatureto warm to 25° C.
stirringstirred for 15 min
additionThe reaction was poured onto ice
filtrationThe resulting tan precipitate was filtered
washwashed with water
customair-dried
customto afford a tan solid
filtrationhot-filtered
concentrationthe filtrate concentrated

Sources & evidence

ORD record: ord-bc5a9195e73d40d39b52587fe246630d
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101634B2

Reaction notes

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