Water → 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-1-(hydroxymethyl)cyclobutanol
Reaction equation
C1C[O:4]CC1.[Cl:6][C:7]1[C:8]2[N:9]([C:13]([CH:16]3[CH2:19][C:18](=[CH2:20])[CH2:17]3)=[N:14][CH:15]=2)[CH:10]=[CH:11][N:12]=1.C[N+]1([O-])CCOCC1.S([O-])([O-])=O.[Na+].[Na+].[OH2:35]>>[Cl:6][C:7]1[C:8]2[N:9]([C:13]([CH:16]3[CH2:19][C:18]([CH2:20][OH:4])([OH:35])[CH2:17]3)=[N:14][CH:15]=2)[CH:10]=[CH:11][N:12]=1Participants
Procedure
To a THF solution (170 mL) of 8-chloro-3-(3-methylene-cyclobutyl)-imidazo[1,5-a]pyrazine (3.1 g, 14 mmol), water (18 mL), 50% N-methylmorpholine-N-oxide in water (3.2 mL) and potassium osmate, dehydrate (200 mg, 0.70 mmol) were added and the reaction was allowed to stir at rt for 4 h. Sodium sulfite (8.0 g, 70.0 mmol) was added to the reaction mixture and allowed to stir for 30 min at which point the reaction was concentrated in vacuo. The crude product was extracted from the aqueous with EtOAc. The organics were washed with brine and the combined aqueous washes were back extracted with EtOAc (5×50 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo to yield the title compounds as a sticky tan/off-white solid; MS (ES+): m/z 254.17 (100) [MH+], 256.19 (50) [MH+++]; HPLC: tR=1.95 min (OpenLynx, polar—5 min).
Workup
- stirringto stir for 30 min at which
- concentrationwas concentrated in vacuo
- extractionThe crude product was extracted from the aqueous with EtOAc
- washThe organics were washed with brine
- extractionthe combined aqueous washes were back extracted with EtOAc (5×50 mL)
- dry with materialThe combined organics were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-af057f5c2979464d810f72870678601a
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08653268B2
Reaction notes
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