Sodium hydride → HCID 86603443, compound

HRID 1994649Notes

Reaction equation

HRID 1994649 reaction equation
[F:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[CH:21]2[N:25]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:24](=[O:35])[NH:23][CH2:22]2)=[C:4]([O:36][CH3:37])[CH:3]=1.[H-].[Na+].[F:40][C:41]([F:55])([F:54])[C:42]1[CH:43]=[C:44]([CH:47]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:49]=1)[CH2:45]Br>CN(C=O)C>[F:40][C:41]([F:54])([F:55])[C:42]1[CH:43]=[C:44]([CH:47]=[C:48]([C:50]([F:53])([F:51])[F:52])[CH:49]=1)[CH2:45][N:23]1[CH2:22][CH:21]([C:12]2[CH:13]=[C:14]([C:17]([F:20])([F:18])[F:19])[CH:15]=[CH:16][C:11]=2[C:5]2[CH:6]=[C:7]([CH:8]([CH3:9])[CH3:10])[C:2]([F:1])=[CH:3][C:4]=2[O:36][CH3:37])[N:25]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[C:24]1=[O:35]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 59135248HCID 59135248, compound2×

Product 1

HCID 86603443HCID 86603443, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 19 mg of 5-[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]-1-(4-methoxybenzyl)imidazolidin-2-one (INTERMEDIATE 32) in 1 mL of DMF was added 3 mg of NaH (60% dispersion in oil). The solution was stirred for 10 min at 0° C. and then 8 μL of 3,5-bistrifluoromethylbenzyl bromide was added and the mixture was stirred for 3 h at 0° C. The reaction mixture was quenched with a drop of water and then filtered and purified by reverse-phase HPLC [Waters XTerra C8 19×50 mm column, eluting at 20 mL/min with 90% water (0.1% TFA) to 100% acetonitrile (0.1% TFA) over 5.15 min, hold for 1.45 min, then back to 90% water over 0.5 min] to provide the title compound. Mass spectrum (ESI) 743.2 (M+1).

Workup

  1. stirringthe mixture was stirred for 3 h at 0° C
  2. customThe reaction mixture was quenched with a drop of water
  3. filtrationfiltered
  4. custompurified by reverse-phase HPLC [Waters XTerra C8 19×50 mm column
  5. washeluting at 20 mL/min with 90% water (0.1% TFA) to 100% acetonitrile (0.1% TFA) over 5.15 min
  6. waithold for 1.45 min

Sources & evidence

ORD record
ord-2f515a87faed4e78892500f82cbd001e
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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