Triethylamine → Ethyl 4-((R)-(2,4-difluorophenyl)((R)-1,1-dimethylethylsulfinamido)methyl)-phenyl(methyl)phosphinate

HRID 1525264Notes

Reaction equation

HRID 1525264 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2[F:23])[NH:9][S@@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:24][PH:25]([O-])([O-:29])[O:26][CH2:27][CH3:28].CCN(CC)CC>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:23][C:17]1[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:16]=1[C@H:8]([NH:9][S@@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])[C:5]1[CH:6]=[CH:7][C:2]([P:25]([CH3:24])(=[O:29])[O:26][CH2:27][CH3:28])=[CH:3][CH:4]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 89462573(R)-N-((R)-(4-bromophenyl)(2,4-difluorophenyl)methyl)-2-methylpropane-2-sulfinamide2×HCID 178476778HCID 178476778, compound

Product 1

HCID 117702173Ethyl 4-((R)-(2,4-difluorophenyl)((R)-1,1-dimethylethylsulfinamido)methyl)-phenyl(methyl)phosphinateYield 81%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To (R)—N—((R)-(4-bromophenyl)(2,4-difluorophenyl)methyl)-2-methylpropane-2-sulfinamide, 20-c, (1 g, 2.5 mmol), ethyl methylphosphite (0.54 g, 5 mmol) and Et3N (0.63 g, 6.25 mmol) in THF (10 ml) was added PdCl2(dppf) (183 mg). The mixture was allowed to stir overnight at reflux. The mixture was filtered and the filtrate was concentrated under vacuum. The residue was taken into ethyl acetate and washed with brine. The organic layer was concentrated under vacuum and the residue was purified over silica gel to give compound, 20-d, (dichloromethane:methanol=50/1) to provide the product (866 mg, 81%).

Workup

  1. temperatureat reflux
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated under vacuum
  4. washwashed with brine
  5. concentrationThe organic layer was concentrated under vacuum
  6. customthe residue was purified over silica gel
  7. customto give compound, 20-d, (dichloromethane:methanol=50/1)

Sources & evidence

ORD record
ord-0fea72cf80e64579b5834d6640cad64e
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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