Acetic Anhydride → HCID 70358071, compound

HRID 1762590Notes

Reaction equation

HRID 1762590 reaction equation
[ClH:1].[CH2:2]([O:4][C:5]([C@H:7]1[C@@H:12]([OH:13])[CH2:11][CH2:10][N:9]([CH2:14][C:15]2[C:18]3[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:17]=3[CH:16]=2)[CH2:8]1)=[O:6])[CH3:3].[C:25](OC(=O)C)(=[O:27])[CH3:26].[OH-].[Na+]>C1(C)C=CC=CC=1>[ClH:1].[CH2:2]([O:4][C:5]([C@H:7]1[C@@H:12]([O:13][C:25](=[O:27])[CH3:26])[CH2:11][CH2:10][N:9]([CH2:14][C:15]2[C:18]3[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:17]=3[CH:16]=2)[CH2:8]1)=[O:6])[CH3:3]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 70358068HCID 70358068, compound

Product 1

HCID 70358071HCID 70358071, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2 g (5.6 mmol) of cis-4-hydroxy-1-[(5-methoxybenzocyclobuten-1-yl)methyl]-piperidine-3-carboxylic acid ethyl ester hydrochloride and 20 ml of acetic anhydride are heated under reflux in 100 ml of toluene for 18 hours. 200 ml of ice-water are then added to the cooled reaction mixture and the whole is stirred for 30 minutes. The reaction mixture is rendered alkaline to pH 10 with 2N sodium hydroxide solution and the toluene phase is then separated off. The aqueous phase is extracted twice with dichloromethane. The organic phases are combined, dried over sodium sulphate and concentrated by evaporation. The crude product so obtained is purified by chromatography over the 10-fold amount of silica gel with diethyl ether as eluant. The purified product is converted into the hydrochloride and crystallised from ethanol/diethyl ether. Cis-4-acetoxy-1-[(5-methoxybenzocyclobuten-1-yl)methyl]-piperidine-3-carboxylic acid ethyl ester hydrochloride of m.p. 202°-203° is obtained.

Workup

  1. customthe toluene phase is then separated off
  2. extractionThe aqueous phase is extracted twice with dichloromethane
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated by evaporation
  5. customThe crude product so obtained
  6. customis purified by chromatography over the 10-fold amount of silica gel with diethyl ether as eluant
  7. customcrystallised from ethanol/diethyl ether

Sources & evidence

ORD record
ord-5ffc59e1f62547709c0905bd1eb4eaef
Source dataset
uspto-grants-1989_05
Patent number
US04833169

Reaction notes

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