Boron trifluoride etherate → (r)-n-(1-(4-Fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide

HRID 1993624Notes

Reaction equation

HRID 1993624 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)=[N:9][S@@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])=[CH:4][C:3]=1[O:30][CH3:31].B(F)(F)F.CCOCC.[CH2:41]([Mg]Cl)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([NH:9][S@@:10]([C:12]([CH3:13])([CH3:14])[CH3:15])=[O:11])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[CH:4][C:3]=1[O:30][CH3:31]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 86612971(R)-N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamideHCID 178418336HCID 178418336, compound

Product 1

HCID 87166154(r)-n-(1-(4-Fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-N-((4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide (4.4 g, 9.42 mmol) in CH2Cl2 (190 mL, 0.05 M) at −71° C. was added BF3.Et2O (2.37 mL, 18.8 mmol). The reaction mixture was stirred for 10 min and BnMgCl (25 mL, 1N in Et2O, 26 mmol) was added. The reaction mixture was stirred at −75° C. for an additional 5 min, and quenched by the addition of saturated NH4Cl. The organic portion was separated, washed by H2O, dried over Na2SO4 and filtered. The solvent was then removed under reduced pressure and the residue was purified by ISCO chromatography using hexanes/EtOAc (0-80%) to give (R)-N-(1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide as a mixture of two diastereomers. The mixture (1 to 4 ratio) was then separated by chiral AD column using 20% IPA/hep/0.15 DEA as mobile phase to afford (R)-N-((S)-1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide (0.79 g, 15% yield). LCMS: RT=2.09 min, [M+H] 560.2 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm).

Workup

  1. stirringThe reaction mixture was stirred at −75° C. for an additional 5 min
  2. customquenched by the addition of saturated NH4Cl
  3. customThe organic portion was separated
  4. washwashed by H2O
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customThe solvent was then removed under reduced pressure
  8. customthe residue was purified by ISCO chromatography

Sources & evidence

ORD record
ord-d30a590fd3e642f7994484f80db4fe5c
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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