Methyl iodide → Methyl-[2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester

HRID 1295352Notes

Reaction equation

HRID 1295352 reaction equation
[C:1]([O:5][C:6](=[O:30])[NH:7][C:8]12[CH2:13][CH:12]1[CH2:11][N:10]([S:14]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH:9]2[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:33]I>CN(C=O)C>[C:1]([O:5][C:6](=[O:30])[N:7]([CH3:33])[C:8]12[CH2:13][CH:12]1[CH2:11][N:10]([S:14]([C:17]1[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=1)(=[O:16])=[O:15])[CH:9]2[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69337282Racemic [2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester2×

Product 1

HCID 69336275Methyl-[2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl esterYield 105.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

The starting material, racemic [2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester (Intermediate 8) (0.6 g, 1.4 mmol) was slurried in DMF (5 mL) and the mixture was cooled to 0° C. Sodium hydride (oil free, 0.05 g, 2.1 mmol) was added in portions and the reaction was then stirred for 0.75 hours at room temperature. Methyl iodide (0.13 mL, 2.1 mmol) was added and the reaction stirred an additional hour at room temperature. The mixture was partitioned between 1N lithium chloride solution and EtOAc. The organics were washed with brine and dried over calcium sulfate, filtered and concentrated to give methyl-[2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester as a yellow crystalline solid (0.654 g, 105%) which contained approximately 0.33 mol % of DMF by 1HNMR.

Workup

  1. stirringthe reaction stirred an additional hour at room temperature
  2. customThe mixture was partitioned between 1N lithium chloride solution and EtOAc
  3. washThe organics were washed with brine
  4. dry with materialdried over calcium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9be31b6dbfe14b48b4f26cc1c9a2dcb5
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

Loading…