Sodium Hydroxide → 4-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1402115Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[C:10]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH:24]=O)[CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C(OI(C1C=CC=CC=1)OC(=O)C)(=O)C.[OH-].[Na+]>CCO.C(Cl)Cl.CO>[C:13]([O:12][C:10]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][C:24]2[N:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]3=[N:8][N:9]=2)[CH2:19][CH2:18]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 0 °C

Procedure

A dark brown solution of (5-fluoro-pyridin-2-yl)-hydrazine (549 mg, 4.32 mmol) and N-Boc-4-piperidine acetaldehyde (Aldrich, 982 mg, 4.32 mmol) in EtOH (10 mL) was stirred at reflux for 30 min, then cooled to 0° C., diluted with DCM (25 mL) and then (diacetoxyiodo)benzene (1.67 g, 5.18 mmol) was added portionwise over 1 min. The purple solution was stirred at RT for 30 min, then aqueous NaOH (1M, 20 mL) was added and the mixture shaken. The aqueous layer was extracted with DCM (2×20 mL), then the combined organics passed through a hydrophobic frit and concentrated in vacuo to leave an orange solid. FCC, using 3% MeOH in DCM, gave the title compound as a pale orange solid (1.53 g, 90%). LCMS (Method 3): Rt 3.15, m/z 235 [M-CO2C4H9+H+].

Workup

temperatureat reflux for 30 min
stirringthe mixture shaken
extractionThe aqueous layer was extracted with DCM (2×20 mL)
concentrationconcentrated in vacuo
customto leave an orange solid

Sources & evidence

ORD record: ord-48ca99761b764e1bb7b8b67b46fbe1fa
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08907094B2

Reaction notes

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