Methyl iodide → [(1R,2S)-3-(2-tert-Butylcarbamoyl-5-chloro-phenyl)-1-(2-fluoro-benzyl)-2-methoxy-propyl]-carbamic acid tert-butyl ester

HRID 658543Notes

Reaction equation

HRID 658543 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[F:33])[C@@H:9]([OH:25])[CH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[C:18](=[O:24])[NH:19][C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:37]I>C1COCC1>[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[F:33])[C@@H:9]([O:25][CH3:37])[CH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[C:18](=[O:24])[NH:19][C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69242992[(1R,2S)-3-(2-tert-Butylcarbamoyl-5-chloro-phenyl)-1-(2-fluoro-benzyl)-2-hydroxy-propyl]-carbamic acid tert-butyl ester

Product 1

HCID 69244332[(1R,2S)-3-(2-tert-Butylcarbamoyl-5-chloro-phenyl)-1-(2-fluoro-benzyl)-2-methoxy-propyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [(1R,2S)-3-(2-tert-Butylcarbamoyl-5-chloro-phenyl)-1-(2-fluoro-benzyl)-2-hydroxy-propyl]-carbamic acid tert-butyl ester (0.40 g, 0.81 mmol) in 5 mL of THF is added a 60% dispersion of sodium hydride in mineral oil (64 mg, 1.6 mmol) and the reaction is allowed to stir for 20 minutes at room temperature. Methyl iodide (0.05 mL, 0.81 mmol) is added and stirring is continued for an additional hour. The reaction is quenched by addition of water and the product is extracted into dichloromethane. The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the resultant crude residue by silica gel flash column chromatography gives the title compound.

Workup

  1. stirringstirring
  2. waitis continued for an additional hour
  3. customThe reaction is quenched by addition of water
  4. extractionthe product is extracted into dichloromethane
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the resultant crude residue by silica gel flash column chromatography

Sources & evidence

ORD record
ord-29376d6c524a4a76be19ce938314554c
Source dataset
uspto-grants-2011_12
Patent number
US08076514B2

Reaction notes

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