Methyl iodide → HCID 70498458, compound

HRID 1424739Notes

Reaction equation

HRID 1424739 reaction equation
[F:1][C:2]([F:30])([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[H-].[Na+].I[CH3:34]>CN(C=O)C>[CH3:34][N:21]([C:18]1[CH:19]=[CH:20][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:29])[F:30])=[CH:9][CH:8]=3)[N:11]=2)=[CH:16][CH:17]=1)[C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68172857HCID 68172857, compound

Product 1

HCID 70498458HCID 70498458, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl (4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamate (120 mg, 0.286 mmol) was dissolved in anhydrous DMF (2.0 mL) under N2 and cooled to 0° C. NaH (60% suspension in mineral oil; 15 mg, 0.372 mmol) was added, and the mixture was stirred for 10 min at 0° C. Iodomethane (23 μL, 0.372 mmol) was added, and the mixture was warmed to ambient temperature and stirred for 1 h. The mixture was quenched with aqueous NH4Cl and extracted with 80% EtOAc/hexanes (×3). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The crude product was applied to a silica gel column, and elution with a 15% to 40% to 80% EtOAc/hexanes gradient provided the title compound (108.0 mg, 87%) as a white solid: mp 125-128° C.; 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.14 (d, J=8.6 Hz, 2H), 7.79 (d, J=8.9 Hz, 2H), 7.38 (d, J=9.8 Hz, 2H), 7.35 (d, J=8.8 Hz, 2H), 3.31 (s, 3H), 1.47 (s, 9H); HRMS-FAB (m/z) [M+H]+ calcd for C21H21F3N4O3, 434.156. found, 434.157.

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for 1 h
  3. customThe mixture was quenched with aqueous NH4Cl
  4. extractionextracted with 80% EtOAc/hexanes (×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. washThe crude product was applied to a silica gel column, and elution with a 15% to 40% to 80% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-36731f02cfaa47d496767f27639a5061
Source dataset
uspto-grants-2015_01
Patent number
US08927729B2

Reaction notes

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