Sodium hydride → Methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate

HRID 1712765Notes

Reaction equation

HRID 1712765 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:15]2[CH:20]=[C:19]([O:21][C:22]([F:27])([F:26])[CH:23]([F:25])[F:24])[CH:18]=[C:17]([F:28])[CH:16]=2)[C:11]([O:13][CH3:14])=[O:12])=[CH:6][C:5]=1[C:29]([F:32])([F:31])[F:30].[Br:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38]Br)=[CH:36][CH:35]=1>CN(C=O)C>[Br:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][C:10]([C:7]2[CH:8]=[CH:9][C:4]([F:3])=[C:5]([C:29]([F:32])([F:30])[F:31])[CH:6]=2)([C:15]2[CH:20]=[C:19]([O:21][C:22]([F:26])([F:27])[CH:23]([F:24])[F:25])[CH:18]=[C:17]([F:28])[CH:16]=2)[C:11]([O:13][CH3:14])=[O:12])=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 685274-Bromobenzyl bromideHCID 59459376Methyl 2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)acetate

Product 1

HCID 86613055Methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoateYield 104.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (60% in oil, 66 mg, 1.65 mmol) in DMF (3 mL) at 0° C. was added a solution of methyl 2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)acetate (600 mg, 1.34 mmol) in one portion. The reaction mixture was stirred at 0° C. for 10 min followed by addition of a solution of 4-bromobenzylbromide (343 mg, 1.37 mmol) in DMF (2 mL). The reaction was stirred at 0° C. for 5 min and quenched by the addition of saturated NH4Cl. The mixture was extracted with EtOAc (2×30 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate as a colorless oil (865 mg, 100% yield). LCMS: RT=2.26 min, no ionization (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.1% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); HPLC: RT=4.48 min (Phenomenex Luna C18 4.6×50 mm column, eluting with 10-90% MeOH/H2O containing 0.2% PPA, flow rate 4 mL/min, wavelength 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 7.29-7.33 (1H, m), 7.21-7.27 (4H, m), 7.11 (1H, t, J=9.23 Hz), 6.94 (1H, d, J=8.79 Hz), 6.82 (1H, d, J=9.67 Hz), 6.80 (1H, s), 6.52 (2H, d, J=8.35 Hz), 5.87 (1H, t, J=53.2 Hz), 3.75 (3H, s), 3.56-3.66 (2H, m).

Workup

  1. stirringThe reaction was stirred at 0° C. for 5 min
  2. customquenched by the addition of saturated NH4Cl
  3. extractionThe mixture was extracted with EtOAc (2×30 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8a7187db1cad4d0ca930507214476158
Source dataset
uspto-grants-2010_09
Patent number
US07790770B2

Reaction notes

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