Water → HCID 86680037, compound

HRID 1915828Notes

Reaction equation

HRID 1915828 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[CH3:9][N:10]1[C:14]([N:15]2[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]2)=[C:13]([N+:22]([O-:24])=[O:23])[CH:12]=[N:11]1.O>CS(C)=O>[CH3:9][N:10]1[C:14]([N:15]2[CH2:16][CH2:17][C:18]3([O:21][CH2:4]3)[CH2:19][CH2:20]2)=[C:13]([N+:22]([O-:24])=[O:23])[CH:12]=[N:11]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 71743244HCID 71743244, compound

Product 1

HCID 86680037HCID 86680037, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Sodium hydride (255 mg, 6.38 mmol) was added portionwise to DMSO (15 mL) at 0° C. The reaction mixture was warmed to room temperature and stirred for 15 min before trimethyl sulfoxonium iodide (1.34 g, 6.09 mmol) was added. After stirring at 90 min at room temperature, a solution of 1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidin-4-one (1.3 g, 5.80 mmol) in DMSO (15 mL) was added. The mixture was heated at 55° C. for 2 hr, then poured into water (200 mL) and extracted with EtOAc (3×80 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to give 6-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1-oxa-6-azaspiro[2.5]octane as an orange liquid. To a solution of this liquid (1.38 g, 5.80 mmol) in MeOH (25 mL) and water (5 mL) was added ammonium chloride (768 mg, 14.4 mmol) followed by sodium azide (1.9 g, 29.2 mmol). The reaction mixture was heated at 70° C. for 18 hr, allowed to cool to room temperature and the MeOH removed under reduced pressure. The residue was diluted with water (20 mL) and extracted with EtOAc (150 mL). The organic layer was washed with water (20 mL) and brine (20 mL), separated, dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (50-75% EtOAc/isohexane) gave 4-(azidomethyl)-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidin-4-ol as yellow oil (1.03 g, 63% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 3.76 (s, 3H), 3.64-3.54 (m, 2H), 3.42 (s, 2H), 3.05-2.96 (m, 2H), 1.92 (s, 1H), 1.81-1.77 (m, 4H).

Workup

  1. additionwas added
  2. temperatureThe mixture was heated at 55° C. for 2 hr
  3. extractionextracted with EtOAc (3×80 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8bc2ab27b3b247ca91586a83e57e7cca
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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