Styrene → HCID 86613061, compound

HRID 1874264Notes

Reaction equation

HRID 1874264 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@@:9]([NH:31][S@@:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33])([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH2:38]=[CH:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C@@:9]([NH:31][S@@:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33])([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:3][C:2]=1[CH:38]=[CH:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

8

Reactant 3

HCID 7501StyreneHCID 11430Potassium CarbonateHCID 59458986HCID 59458986, compound

Product 1

HCID 86613061HCID 86613061, compoundYield 23%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a suspension of Pd(OAc)2 (9 mg, 0.04 mmol) and PPh3 (2 mg, 0.008 mmol) in DMF was added Bu4NBr (265 mg, 0.8 mmol), (R)—N—((S)-1-(3-bromo-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide, prepared as described in Procedure 62, (500 mg, 0.8 mmol), styrene (137 mg, 1.3 mmol) and K2CO3 (136 mg, 1.0 mmol). The reaction mixture was degassed and backfilled with argon several times. The reaction mixture was heated at 85° C. for 16 h. The reaction mixture was then poured into sat. NH4Cl and the aqueous phase was extracted with EtOAc. The combined organic portions were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO chromatography (12 g column, 0-30% EtOAc/hexane) to yield (R)—N—((R)-1-(4-fluoro-3-styrylphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide (119 mg, 23% yield). LCMS: RT=4.62 min [M+H] 632 (Phenomenex Luna C18, 50×4.6 mm, 10%-90% H2O/ACN with 0.1% TFA, 4 min gradient, flow rate 4 mL/min, monitoring at 220 nm).

Workup

  1. customprepared
  2. customThe reaction mixture was degassed
  3. additionThe reaction mixture was then poured into sat. NH4Cl
  4. extractionthe aqueous phase was extracted with EtOAc
  5. dry with materialThe combined organic portions were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by ISCO chromatography (12 g column, 0-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-7a2dd1e18e8346d2bd08255254305e0e
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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