Triethylamine → Ethyl 4-((R)-(4-fluorophenyl)((R)-1-methylethylsulfinamido)-methyl)phenyl(methyl)phosphinate

HRID 1525253Notes

Reaction equation

HRID 1525253 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](C)([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]>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C@@H:8]([NH:9][S@@:10]([CH:12]([CH3:13])[CH3:14])=[O:11])[C:5]2[CH:6]=[CH:7][C:2]([P:24]([CH3:23])(=[O:28])[O:25][CH2:26][CH3:27])=[CH:3][CH:4]=2)=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 89462272(R)-N-((R)-(4-bromophenyl)(4-fluorophenyl)methyl)-2-methylpropane-2-sulfinamide2×HCID 178476778HCID 178476778, compound

Product 1

HCID 117702236Ethyl 4-((R)-(4-fluorophenyl)((R)-1-methylethylsulfinamido)-methyl)phenyl(methyl)phosphinate

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)(4-fluorophenyl)methyl)-2-methylpropane-2-sulfinamide, 18-c, (10 g, 0.026 mol), ethyl methylphosphite (5.6 g, 0.052 mol) and Et3N (7.88 g, 0.078 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, 18-d, (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)
  7. customto provide the product, 18-d, (6.9 g, 68%)

Sources & evidence

ORD record
ord-1451bc4d111347e9ad69cee44fe7bd91
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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