Water → HCID 45275570, compound

HRID 1622371Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:16])[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[N:15])[CH2:10][CH2:9]1.[Li+].[CH3:18]C([N-]C(C)C)C.CI.O>C1COCC1>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:16])[C:7]=1[N:8]1[CH2:13][CH2:12][C:11]([CH3:18])([C:14]#[N:15])[CH2:10][CH2:9]1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-(3,5-dichloropyridin-4-yl)piperidine-4-carbonitrile E48 (90 mg, 0.35 mmol) in THF (1.5 mL), at −78° C., was added a 1M solution of LDA in THF (0.38 mL, 0.38 mmol). The mixture was stirred for 30 min at −78° C. before warming to r.t. After 60 min, methyl iodide (31 μL, 0.5 mmol) was added. The mixture was stirred for a further 60 min at r.t. for 1 h, before addition of water (5 mL). The mixture was extracted with CH2Cl2 (3×5 mL) and the combined organic extracts were dried over MgSO4 and concentrated under reduced pressure to dryness. The crude product was purified by flash column chromatography on silica gel (hexane, EtOAc, 100:0-80:20, biotage 25+M) to furnish the title compound as a white solid (34 mg, 36%), along with recovered 1-(3,5-dichloropyridin-4-yl)piperidine-4-carbonitrile (23 mg, 25%), LC-MS (ESI, 4 min) Rt 3.09 min, m/z 270 (100%, W); m/z (ESI) C12H13Cl2N3 requires 269.0487 found [M+H]+ 289.0488.

Workup

temperaturebefore warming to r.t
waitAfter 60 min
extractionThe mixture was extracted with CH2Cl2 (3×5 mL)
dry with materialthe combined organic extracts were dried over MgSO4
concentrationconcentrated under reduced pressure to dryness
customThe crude product was purified by flash column chromatography on silica gel (hexane, EtOAc, 100:0-80:20, biotage 25+M)

Sources & evidence

ORD record: ord-f5d91f2d341d4fd08c68ad6221ac9613
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778925B2

Reaction notes

Loading…