2-Azido-2-methylpropanoic acid → 2-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoic acid

HRID 877357Notes

Reaction equation

HRID 877357 reaction equation
[CH3:1][C:2]([S:5]([NH:7][C@@H:8]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[CH:13][N:12]=1)[C:9]#[CH:10])=[O:6])([CH3:4])[CH3:3].[N:23]([C:26]([CH3:31])([CH3:30])[C:27]([OH:29])=[O:28])=[N+:24]=[N-:25].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>O.C(O)(C)(C)C.S([O-])([O-])(=O)=O.[Cu+2]>[C:2]([S:5]([NH:7][C@H:8]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]([F:22])([F:20])[F:21])=[CH:13][N:12]=1)[C:9]1[N:25]=[N:24][N:23]([C:26]([CH3:31])([CH3:30])[C:27]([OH:29])=[O:28])[CH:10]=1)=[O:6])([CH3:1])([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 128639852-Azido-2-methylpropanoic acidHCID 23667548Sodium AscorbateHCID 866689592-methyl-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]prop-2-ynyl}propane-2-sulfinamide

Product 1

HCID 681578412-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoic acidYield 44%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of 0.50 g (1.5 mmol) 2-methyl-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]prop-2-ynyl}propane-2-sulfinamide in 3.0 mL water and 3.0 mL t-butanol was added 1.8 mL (1.5 mmol) 2-azido-2-methylpropanoic acid, 0.15 mL (0.15 mmol) 1.0M aqueous sodium ascorbate solution, and 15 μL (0.02 mmol) 1.0M solution of aqueous copper (II) sulfate. After 24 h at room temperature, the reaction mixture was quenched with water, acidified with 1N HCl, extracted three times with ethyl acetate, and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 0-20% MeOH:CH2Cl2) afforded 0.30 g (44%) 2-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoic acid. ES-MS [M+1]+=464.2.

Workup

  1. customthe reaction mixture was quenched with water
  2. extractionextracted three times with ethyl acetate
  3. washwashed with brine
  4. dry with materialThe organic layer was dried over NaSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography (silica gel, linear gradient 0-20% MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-a01cda74f5494766a53ecf3f65f35f0a
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Reaction notes

Loading…