Water → HCID 86680037, compound

HRID 1915830Notes

Reaction equation

HRID 1915830 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 (60% in mineral oil, 200 mg, 4.9 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 (1.0 g, 4.6 mmol) was added. After stirring for 90 min at room temperature, a solution of 1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidin-4-one (1.0 g, 4.45 mmol) in DMSO (15 mL) was added. The mixture was heated at 55° C. for 3 hr, then poured into water (50 mL) and extracted with EtOAc (3×50 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 (0.4 g, 1.67 mmol) in a reaction tube was added a 7 M solution of NH3 in MeOH (20 mL) and the mixture stirred in a sealed tube at room temperature for 24 hr. The reaction mixture was concentrated under reduced pressure and the residue purified via silica gel chromatography (1-10% 7 M NH3 in MeOH/DCM) to give 4-(aminomethyl)-1-(2-methyl-4-nitro-pyrazol-3-yl)piperidin-4-ol as a yellow solid, (350 mg, 60% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 3.76 (s, 3H), 3.64-3.54 (m, 2H), 3.09-3.03 (m, 2H), 2.72 (s, 2H), 1.73-1.62 (m, 4H). Exchangeables not observed.

Workup

  1. additionwas added
  2. temperatureThe mixture was heated at 55° C. for 3 hr
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7194f6b7afc848a1baaa840c4ce61b8b
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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