Methyl iodide → HCID 178476334, compound

HRID 967152Notes

Reaction equation

HRID 967152 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([CH2:17][O:18][C:19](=[O:21])[CH3:20])[CH2:13][CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22]I.[H-].[Na+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]([CH3:22])[CH2:9][CH2:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([CH2:17][O:18][C:19](=[O:21])[CH3:20])[CH2:13][CH2:12]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 178476335HCID 178476335, compound

Product 1

HCID 178476334HCID 178476334, compoundYield 68.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice-cooled and stirred solution of the crude 26.0 g trans-acetic acid 4-(2-tert-butoxycarbonylamino-ethyl)-cyclohexylmethyl ester and 5.77 ml (92.6 mmol) methyliodide in 300 ml of N,N-dimethylformamide was added within 15 minutes 4.04 g (92.58 mmol) sodium hydride (55% in oil). After stirring over night at room temperature, additional 1.65 ml (26.5 mmol) methyliodide and 1.16 g (26.5 mmol) of sodium hydride were added and the reaction-mixture was then stirred for another 1 hour at room temperature. It was then partitioned between ether, 1N hydrogen chloride solution and water. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure and the residue then chromatographed on silica gel with a 4:1 v/v mixture of hexane and ethylacetate as the eluent giving 18.7 g (67.7% over 3 steps) of pure trans-acetic acid 4-[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-cyclohexylmethyl ester as colorless viscous oil, MS: 214 [(M-(tert-butoxycarbonyl))H+].

Workup

  1. stirringthe reaction-mixture was then stirred for another 1 hour at room temperature
  2. customIt was then partitioned between ether, 1N hydrogen chloride solution and water
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customthe residue then chromatographed on silica gel with a 4:1 v/v mixture of hexane and ethylacetate as the eluent

Sources & evidence

ORD record
ord-a9fabeab1da8468e809725784e798115
Source dataset
uspto-grants-2005_10
Patent number
US06953806B2

Reaction notes

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