Iodoethane → HCID 86668346, compound

HRID 1424738Notes

Reaction equation

HRID 1424738 reaction equation
[F:1][C:2]([F:38])([F:37])[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:36])[O:23][CH:24]([C:26]4[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=4)[CH3:25])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[H-].[Na+].I[CH2:42][CH3:43]>CN(C=O)C>[CH2:42]([N:21]([C:18]1[CH:17]=[CH:16][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:37])[F:38])=[CH:5][CH:6]=3)[N:11]=2)=[CH:20][CH:19]=1)[C:22](=[O:36])[O:23][CH:24]([C:26]1[CH:27]=[N:28][C:29]([C:32]([F:34])([F:35])[F:33])=[CH:30][CH:31]=1)[CH3:25])[CH3:43]

Participants

5

Reactant 3

HCID 6340Iodoethane2×HCID 24758Sodium hydride2×HCID 86668347HCID 86668347, compound

Product 1

HCID 86668346HCID 86668346, compoundYield 92.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-(6-(Trifluoromethyl)pyridin-3-yl)ethyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenylcarbamate (54 mg, 0.10 mmol) was dissolved in anhydrous DMF (0.5 mL) under N2 and cooled to 0° C. NaH (60% suspension in mineral oil; 4.4 mg, 0.11 mmol) was added, and the mixture was stirred for 10 min at 0° C. Iodoethane (9 μL, 0.11 mmol) was added, and the mixture was warmed to ambient temperature and stirred for 1 h. Additional NaH (4 mg) and iodoethane (5 μL) were added at ambient temperature to promote complete consumption of the starting material. 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 (52.1 mg, 91%) as a light yellow oil: IR 3111, 2983, 2936, 1707, 1519, 1340, 1268, 1155 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.62 (s, J=10.6 Hz, 1H), 8.58 (s, 1H), 8.21 (d, J=8.5 Hz, 2H), 7.81 (d, J=9.0 Hz, 2H), 7.73-7.58 (m, 2H), 7.40 (d, J=8.5 Hz, 2H), 7.30 (d, J=8.5 Hz, 2H), 5.95 (q, J=6.6 Hz, 1H), 3.84-3.70 (m, 2H), 1.53 (d, J=6.2 Hz, 3H), 1.19 (t, J=7.1 Hz, 3H); HRMS-FAB (m/z) [M+H]+ calcd for C26H21F6N5O3, 565.1549. found, 565.1568.

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for 1 h
  3. customconsumption of the starting material
  4. customThe mixture was quenched with aqueous NH4Cl
  5. extractionextracted with 80% EtOAc/hexanes (×3)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. 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-2c22eac401664b3eac9490b1d75fe9f7
Source dataset
uspto-grants-2015_01
Patent number
US08927729B2

Reaction notes

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