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Methanol → tert-butyl 4-[5-(6-methoxypyridin-3-yl)-4H-1,2,4-triazol-3-yl]piperidine-1-carboxylate

HRID 605014
Notes
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Reaction equation

HRID 605014 reaction equation
[NH:1]([C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)=O)[NH2:2].CO[C:20]1[CH:21]=[C:22]([C:26]#[N:27])[CH:23]=[N:24][CH:25]=1.[CH3:28][O-:29].[Na+].CO>C(OCCO)C.C(O)(=O)C>[CH3:28][O:29][C:25]1[N:24]=[CH:23][C:22]([C:26]2[NH:27][C:3]([CH:5]3[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]3)=[N:1][N:2]=2)=[CH:21][CH:20]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 22713165tert-Butyl 4-(hydrazinecarbonyl)piperidine-1-carboxylateHCID 231597785-Methoxypyridine-3-carbonitrile

Product 1

HCID 178489121tert-butyl 4-[5-(6-methoxypyridin-3-yl)-4H-1,2,4-triazol-3-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 176
Acetic Acid
Solvent
HCID 8076Glycol monoethyl etherSolvent

Conditions

Temperature
130 °C

Procedure

tert-Butyl 4-(hydrazinocarbonyl)-piperidine-1-carboxylate (800 mg, 3.29 mmol) was dissolved in anhydrous 2-ethoxyethanol (10 mL) and 5-methoxypyridine-3-carbonitrile (662 mg, 4.9 mmol) was added to the solution. A solution of 0.5M sodium methoxide in methanol (3 mL, ˜1.5 mmol) was added and the mixture was heated at 130° C. for 16 h. The cooled reaction mixture was neutralized with acetic acid and partitioned between ethyl acetate and aq. NaHCO3. The organic layer was dried over Na2SO4, the salts removed by filtration and the solvent evaporated under vacuum. This residue was triturated with diethyl ether to give tert-butyl 4-[5-(6-methoxypyridin-3-yl)-4H-1,2,4-triazol-3-yl]piperidine-1-carboxylate as a white solid. This material was dissolved in methylene chloride (10 mL) and TFA (10 mL) was added. After one hour the solvent was evaporated under reduced pressure to give 2-methoxy-5-(5-piperidin-4-yl-4H-1,2,4-triazol-3-yl)pyridine. NMR (MeOD): δ 8.75 (1H, s), 8.19 (1H, d, J=6 Hz), 6.93 (1H, d, J=6 Hz), 3.95 (3H, s), 3.51 (2H, m), 3.22 (3H, m), 2.32 (2H, m), 2.11 (2H, m).

Workup

  1. customThe cooled reaction mixture
  2. custompartitioned between ethyl acetate and aq. NaHCO3
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customthe salts removed by filtration
  5. customthe solvent evaporated under vacuum
  6. customThis residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-07bdc3c61365467cab3a7c1749673ca9
Source dataset
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07910561B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes