Potassium Phosphate, Tribasic → N-(1-(3-(3,5-difluorophenyl)-benzo[b]thiophen-2-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 2036601Notes

Reaction equation

HRID 2036601 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([F:8])[CH:7]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.Br[C:50]1[C:51]2[CH:67]=[CH:66][CH:65]=[CH:64][C:52]=2[S:53][C:54]=1[CH:55]([NH:57][S:58]([C:60]([CH3:63])([CH3:62])[CH3:61])=[O:59])[CH3:56]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:50]2[C:51]3[CH:67]=[CH:66][CH:65]=[CH:64][C:52]=3[S:53][C:54]=2[CH:55]([NH:57][S:58]([C:60]([CH3:62])([CH3:63])[CH3:61])=[O:59])[CH3:56])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 58459232N-(1-(3-bromobenzo[b]thiophen-2-yl)ethyl)-2-methylpropane-2-sulfinamide

Product 1

HCID 58459329N-(1-(3-(3,5-difluorophenyl)-benzo[b]thiophen-2-yl)ethyl)-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3,5-difluorophenylboronic acid (292 mg, 1.848 mmol), potassium phosphate (0.204 mL, 2.464 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (126 mg, 0.308 mmol), palladium (II) acetate (27.7 mg, 0.123 mmol) and N-(1-(3-bromobenzo[b]thiophen-2-yl)ethyl)-2-methylpropane-2-sulfinamide (444 mg, 1.232 mmol) in Toluene (10 mL) was purged with N2 for 2 min, then heated to 110° C. overnight. After 19 h, the reaction was partitioned between water and EtOAc. The organic layer was stirred over MgSO4, filtered and concentrated under reduced pressure to give amber oil. The product was purified by column chromatography on a silica gel column using 20 to 40% gradient of EtOAc in hexane as eluent to give N-(1-(3-(3,5-difluorophenyl)benzo[b]thiophen-2-yl)ethyl)-2-methylpropane-2-sulfinamide as a colorless glassy solid: 1H NMR (400 MHz, DMSO-d6) δ 1.13 (s, 9H), 1.50 (d, J=6.7 Hz, 3H), 4.64-4.73 (m, 1H), 5.91 (d, J=4.7 Hz, 1H), 7.21 (dd, J=8.4, 2.3 Hz, 2H), 7.34-7.45 (m, 4H), 8.02 (ddd, J=7.5, 1.4, 1.1 Hz, 1H); LC-MS (ESI)] m/z 394.0 [M+H]+.

Workup

  1. customwas purged with N2 for 2 min
  2. customthe reaction was partitioned between water and EtOAc
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give amber oil
  6. customThe product was purified by column chromatography on a silica gel column

Sources & evidence

ORD record
ord-e8d0327624484013afff11be16dd538f
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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