Triethylamine → Ethyl 4-((S)-((S)-1,1-dimethylethylsulfinamido)(4-fluorophenyl)-methyl)phenyl(methyl)phosphinate

HRID 1525259Notes

Reaction equation

HRID 1525259 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][CH:17]=2)[NH:9][S@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:23][PH:24]([O-])([O-:28])[O:25][CH2:26][CH3:27].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]>[CH3:13][C:12]([CH3:15])([S@@:10]([NH:9][C@@H:8]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[C:5]1[CH:6]=[CH:7][C:2]([P:24]([CH3:23])(=[O:28])[O:25][CH2:26][CH3:27])=[CH:3][CH:4]=1)=[O:11])[CH3:14]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 89464549(S)-N-((S)-(4-bromophenyl)(4-fluorophenyl)methyl)-2-methylpropane-2 sulfinamide2×HCID 178476778HCID 178476778, compound

Product 1

HCID 89472221Ethyl 4-((S)-((S)-1,1-dimethylethylsulfinamido)(4-fluorophenyl)-methyl)phenyl(methyl)phosphinateYield 68%

Reagents, catalysts & solvents 2

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

Procedure

To (S)—N—((S)-(4-bromophenyl)(4-fluorophenyl)methyl)-2-methylpropane-2-sulfinamide, 19-b, (10 g, 0.026 mol), ethyl methylphosphite (5.6 g, 0.052 mol) and Et3N (7.88 g, 0.78 mol) in THF (100 ml) was added PdCl2(dppf) (2.2 g). 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 dichloromethane and washed with brine. The organic layer was concentrated under vacuum and the residue was purified over silica gel (petroleum ether:ethyl acetate=1/1) to provide the product, 19-c, (6.9 g, 68%).

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 (petroleum ether:ethyl acetate=1/1)

Sources & evidence

ORD record
ord-d937aa2981a3418ea0c9f30e7efbbc17
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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