Hydrochloric Acid → 1-[(3-Methoxyphenyl)methyl]piperidin-4-one
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[CH2:6][N:7]1[CH2:16][CH2:15][C:10]2(OCC[O:11]2)[CH2:9][CH2:8]1.Cl>[OH-].[Na+]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[CH2:6][N:7]1[CH2:8][CH2:9][C:10](=[O:11])[CH2:15][CH2:16]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 8-(3-methoxybenzyl)-1,4-dioxa-8-azaspiro[4.5]decane (16.0 g, 60.76 mmol) from Step A above was added an ice-cold solution of concentrated hydrochloric acid (320 mL). The suspension was stirred at 0° C. for 5 min and then allowed to warm to ambient temperature. After 1 h, the homogeneous solution was poured into a sodium hydroxide solution (21.5 g in 200 mL of water) at 0° C. and then extracted with methylene chloride (2×150 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (methylene chloride to 1:1 ethyl acetate/methylene chloride) gave 1-(3-methoxybenzyl)piperidin-4-one (11.0 g, 83%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 7.28-7.22 (m, 1H), 6.97-6.90 (m, 2H), 6.82 (dd, J=2.1, 7.9 Hz, 1H), 3.82 (s, 3H), 3.60 (s, 2H), 2.75 (t, J=6.1 Hz, 4H), 2.46 (t, J=6.1 Hz, 4H); ESI MS (m/z) 220 [M+H].
Workup
- temperatureto warm to ambient temperature
- waitAfter 1 h
- extractionextracted with methylene chloride (2×150 mL)
- dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
- concentrationconcentrated in vacuo
- customPurification by silica gel chromatography (methylene chloride to 1:1 ethyl acetate/methylene chloride)
Sources & evidence
- ORD record
- ord-43a44166d51b442aafb5d80b08a12aa7
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09045468B2
Reaction notes
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