Water → 1'-benzyl-5-methyl-3H-spiro[1-benzofuran-2,4'-piperidine]

HRID 270038Notes

Reaction equation

[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][C:13]([CH2:17][C:18]2[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=2F)([OH:16])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CN(C=O)C.O>C1(C)C=CC=CC=1>[CH2:3]([N:10]1[CH2:15][CH2:14][C:13]2([CH2:17][C:18]3[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=3[O:16]2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a suspension of NaH (55% in mineral oil, 200 mg, 5 mmol) in toluene (10 mL) was slowly added a solution of crude 1-benzyl-4-(2-fluoro-5-methylbenzyl)piperidin-4-ol in toluene (15 mL). After addition was completed, the reaction mixture was heated to 110° C. and stirred for 5 min. DMF (9 mL) was added and stirring was continued at reflux temperature for 10 h. The reaction mixture was cooled to room temperature, poured into water (50 ml), and extracted with ethyl acetate (2×25 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash chromatography (ethyl acetate/n-heptane) to give the subtitle compound (240 mg, 41%).

Workup

additionAfter addition
stirringstirring
temperatureat reflux temperature for 10 h
temperatureThe reaction mixture was cooled to room temperature
extractionextracted with ethyl acetate (2×25 ml)
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel flash chromatography (ethyl acetate/n-heptane)

Sources & evidence

ORD record: ord-260f62b0aab84857b4fdc4e95d4293a3
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449475B2

Reaction notes

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