Water → 4-(3-Fluoro-5-nitro-phenoxy)-1-methyl-piperidine

HRID 1821989Notes

Reaction equation

[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[H-].[Na+].[F:11][C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[C:14](F)[CH:13]=1.O>CN(C)C=O>[F:11][C:12]1[CH:13]=[C:14]([CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1)[O:8][CH:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1

Participants

Conditions

Temperature: 65 °C

Procedure

Dissolve 1-methyl-piperidin-4-ol (3.62 g, 31.43 mmol) in N,N-dimethylformamide (20 mL) and add 95% sodium hydride (0.83 g, 33.0 mmol) at ambient temperature. After 40 min., add 1,3-difluoro-5-nitro-benzene (5.0 g, 31.43 mmol), stir and heat at 65° C. After 2 hr., cool to ambient temperature and pour slowly into water (100 mL). Extract the reaction mixture with ethyl acetate (3×150 mL), wash the combined organic layers with aqueous NaCl solution (100 mL), dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride to obtain of the title compound (2.76 g, 35%). 1H NMR (CDCl3): 7.6 (s, 1H), 7.5 (d, 1H), 7.0 (d, 1H), 4.4 (m, 1H), 2.7 (m, 2H), 2.4 (m, 5H), 2.0 (m, 2H), 1.9 (m, 2H).

Workup

waitAfter 2 hr
temperature, cool to ambient temperature
extractionExtract the reaction mixture with ethyl acetate (3×150 mL)
washwash the combined organic layers with aqueous NaCl solution (100 mL)
dry with materialdry over sodium sulfate
filtrationfilter
concentrationconcentrate
customPurify the residue by silica gel flash chromatography
washeluting with 10% (2M NH3/methanol)/methylene dichloride

Sources & evidence

ORD record: ord-e1aa9c1c2c024d85abace55206b0f62d
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608629B2

Reaction notes

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