Water → 1-Tert-butoxycarbonyl-4-(4-chlorophenyl)-4-methoxypiperidine

HRID 457119Notes

Reaction equation

HRID 457119 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:24]I.O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)([O:14][CH3:24])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 21997555tert-Butyl 4-(4-chlorophenyl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 219975781-Tert-butoxycarbonyl-4-(4-chlorophenyl)-4-methoxypiperidineYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-Chloro-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (200 mg, 0.641 mmol) was added portionwise as a solid to a suspension of sodium hydride (0.018 g, 0.770 mmol) in dimethylformamide (6 mL) at room temperature. After 30 minutes, methyl iodide (0.109 g, 60 uL, 0.770 mmol) was added and the mixture was stirred overnight. The mixture was poured into an equal volume of water and extracted with ethyl acetate (2×10 mL). The ethyl acetate extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo to give a tan oil. The crude oil was purified by silica gel chromatography (hexane to 60:40 hexane/ethyl acetate gradient) to afford 4-(4-Chloro-phenyl)-4-methoxy-piperidine-1-carboxylic acid tert-butyl ester as a clear oil (108 mg, 52%).

Workup

  1. extractionextracted with ethyl acetate (2×10 mL)
  2. dry with materialThe ethyl acetate extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a tan oil
  6. customThe crude oil was purified by silica gel chromatography (hexane to 60:40 hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-bf717a8da08b4d6eb161840d31d2cc29
Source dataset
uspto-grants-2007_03
Patent number
US07186729B2

Reaction notes

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