p-Toluenesulfonic acid → [2-Methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-carbamic acid tert-butyl ester

HRID 1242481Notes

Reaction equation

HRID 1242481 reaction equation
[CH3:1][C:2]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[CH:8]=[CH:7][C:3]=1C(O)=O.C[O:22][C:23](=[O:41])C1C=CC(C2C=CC(C(F)(F)F)=CC=2)=NC=1C.C([N:44](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:66]1([CH3:76])[CH:71]=CC(S(O)(=O)=O)=C[CH:67]=1>CC(O)(C)C>[C:66]([O:22][C:23](=[O:41])[NH:44][C:3]1[C:2]([CH3:1])=[N:10][C:9]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=2)=[CH:8][CH:7]=1)([CH3:76])([CH3:71])[CH3:67]

Participants

7

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 219358852-Methyl-6-(4-trifluoromethyl-phenyl)-nicotinic acidHCID 67072269HCID 67072269, compound

Product 1

HCID 67072248[2-Methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

4.30 g (15.3 mmol) of 2-methyl-6-(4-trifluoromethyl-phenyl)-nicotinic acid (prepared from 2-methyl-6-(4-trifluoromethyl-phenyl)-nicotinic acid methyl ester (example 1L]) in analogy to the procedure described in example 53B]) was dissolved in 85 ml of 2-methyl-2-propanol and 3.18 ml=2.32 g (22.9 mmol) of triethylamine was added. After 5 min., 4.97 ml=6.64 g (22.9 mmol) of diphenylphosphoryl azide (95%) was added. The reaction mixture was then stirred at reflux (oil bath 100° C.). After 10 min., 0.53 g (3.1 mmol) of anhydrous 4-toluene sulfonic acid was added and stirring continued for 1 hour at reflux. The solvent was then completely removed by evaporation at high vacuum; the residue was dissolved in Et2O and washed with H2O, 1N HCl, and NaHCO3 solution. The combined organic phases were dried over anhydrous magnesium sulfate and evaporated. The crude product was purified by crystallization (EtOAc, n-heptane) to give 4.05 g of the title compound as colorless solid.

Workup

  1. waitAfter 10 min.
  2. stirringstirring
  3. waitcontinued for 1 hour
  4. temperatureat reflux
  5. customThe solvent was then completely removed by evaporation at high vacuum
  6. dissolutionthe residue was dissolved in Et2O
  7. washwashed with H2O, 1N HCl, and NaHCO3 solution
  8. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  9. customevaporated
  10. customThe crude product was purified by crystallization (EtOAc, n-heptane)

Sources & evidence

ORD record
ord-346c8349688345618fe2eb7177d13ab2
Source dataset
uspto-grants-2006_10
Patent number
US07115611B2

Reaction notes

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