Triethylamine → [5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester

HRID 631930Notes

Reaction equation

HRID 631930 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[N:11][N:10]([CH3:13])[C:9]=2C(O)=O)=[CH:4][CH:3]=1.[F:17][C:18]([F:29])([F:28])[C:19]1[CH:20]=[C:21]([C@H:25]([OH:27])[CH3:26])[CH:22]=[CH:23][CH:24]=1.C([N:32]([CH2:35]C)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:44])=CC=1>C1(C)C=CC=CC=1>[F:17][C:18]([F:28])([F:29])[C:19]1[CH:20]=[C:21]([C@H:25]([O:27][C:35](=[O:44])[NH:32][C:9]2[N:10]([CH3:13])[N:11]=[N:12][C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=2)[CH3:26])[CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 2779038(alphaR)-alpha-Methyl-3-(trifluoromethyl)benzenemethanolHCID 712662515-(4-Bromophenyl)-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid

Product 1

HCID 131735432[5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl esterYield 68.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

In a 20 ml, vial, 5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid (114.3 mg, 405 μmol), (R)-1-(3-(trifluoromethyl)phenyl)ethanol (84.8 mg, 446 μmol) and triethylamine (90.2 mg, 124 μL, 891 μmol) were combined with toluene (5 mL) to give a colorless solution and to this was added DPPA (167 mg, 131 μL, 608 μmol). The reaction vial was sealed, heated in a dry block at 65° C. for 3 hr, and allowed to cool to room temperature overnight. The reaction was concentrated, dried from DCM/hexanes, dissolved in minimal DCM and purified by flash chromatography (silica gel, 0% to 60% EtOAc in hexanes). Appropriate fractions were combined, concentrated, dried from DCM/hexanes to yield [5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester (130 mg, 68.4% yield) as a white solid. LC/MS calcd. for C19H16BrF3N4O2 (m/e) 468/470, obsd. 469/471 (M+H, ES+).

Workup

  1. customto give a colorless solution
  2. customThe reaction
  3. customvial was sealed
  4. temperatureto cool to room temperature overnight
  5. concentrationThe reaction was concentrated
  6. dry with materialdried from DCM/hexanes
  7. dissolutiondissolved in minimal DCM
  8. custompurified by flash chromatography (silica gel, 0% to 60% EtOAc in hexanes)
  9. concentrationconcentrated
  10. dry with materialdried from DCM/hexanes

Sources & evidence

ORD record
ord-8039c3d45c014fe5ad038156d3e2c148
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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