Methyl iodide → HCID 59614369, compound

HRID 409463Notes

Reaction equation

HRID 409463 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:19][C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[CH:21]=2)[C:14]2[N:15]=[N:16][NH:17][N:18]=2)[CH2:10][C@H:9]1[CH2:34][CH3:35])=[O:7])([CH3:4])([CH3:3])[CH3:2].CI.[C:38](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:19][C:20]2[CH:25]=[C:24]([C:26]([F:28])([F:27])[F:29])[CH:23]=[C:22]([C:30]([F:32])([F:33])[F:31])[CH:21]=2)[C:14]2[N:15]=[N:16][N:17]([CH3:38])[N:18]=2)[CH2:10][C@H:9]1[CH2:34][CH3:35])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 86648400HCID 86648400, compound

Product 1

HCID 59614369HCID 59614369, compoundYield 86.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the crude (2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(2H-tetrazol-5-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (52 mg, 0.10 mmol), methyl iodide (90 mg, 0.51 mmol) and potassium carbonate (28 mg, 0.20 mmol) in DMF (1.3 mL) is stirred at 50° C. for 2 hours. The reaction mixture is quenched with saturated ammonium chloride solution. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (45 mg, 44% overall yield in 4 steps).

Workup

  1. customThe reaction mixture is quenched with saturated ammonium chloride solution
  2. extractionThe product is extracted three times with EtOAc
  3. washThe combined organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-2cb722a2c6c543bfb9c62407957bdf5b
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

Loading…