Water → 3-(4-Allyloxy-piperidin-1-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

HRID 1402196Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([N:11]3[CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]3)=[N:9][N:10]=2)[CH:7]=1.[H-].[Na+].[CH2:20](Br)[CH:21]=[CH2:22].O>C1COCC1.CCOC(C)=O.CO>[CH2:22]([O:17][CH:14]1[CH2:15][CH2:16][N:11]([C:8]2[N:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]3=[N:10][N:9]=2)[CH2:12][CH2:13]1)[CH:21]=[CH2:20]

Participants

Conditions

Temperature: 0 °C

Procedure

To an opaque pale yellow solution of Intermediate 24c (510 mg, 2.16 mmol) in dry THF at 0° C. under Ar was added NaH (60% dispersion in oil, 216 mg, 5.40 mmol) (CARE: gas evolution) and the resulting suspension was stirred at 0° C. for 30 min. Allyl bromide (0.467 mL, 5.40 mmol) was added and the suspension stirred at RT under Ar for 1 h and at 70° C. for 18 h. Water (25 mL) was added to the cooled solution, then the mixture extracted with EtOAc (3×25 mL). The combined organics were washed with brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo to leave a dark brown oil. FCC, using 0-8% MeOH in EtOAc, gave the title compound as a brown oil (171 mg, 29%). LCMS (Method 3): Rt 2.81 min, m/z 277 [MH+].

Workup

stirringthe suspension stirred at RT under Ar for 1 h and at 70° C. for 18 h
extractionthe mixture extracted with EtOAc (3×25 mL)
washThe combined organics were washed with brine (25 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customto leave a dark brown oil

Sources & evidence

ORD record: ord-3ed15e98a7e3424fb9c09f315571ed53
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08907094B2

Reaction notes

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