(S)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate → (5)-Tert-butyl 3-(3-(but-3-enyl)phenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate

HRID 1471627Notes

Reaction equation

HRID 1471627 reaction equation
I[C:2]1[CH:3]=[C:4]([CH2:8][C@H:9]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:10]([N:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH3:13])=[O:11])[CH:5]=[CH:6][CH:7]=1.[CH2:30]([Mg]Br)[CH2:31][CH:32]=[CH2:33]>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]>[CH2:33]([C:2]1[CH:3]=[C:4]([CH2:8][C@H:9]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:26])[CH3:27])[C:10]([N:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH3:13])=[O:11])[CH:5]=[CH:6][CH:7]=1)[CH2:32][CH:31]=[CH2:30]

Participants

5

Reactant 2

HCID 90289973(S)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamateHCID 178418797HCID 178418797, compound

Product 1

HCID 130272769(5)-Tert-butyl 3-(3-(but-3-enyl)phenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamateYield 62%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of (5)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate (510 mg, 1.0 mmol), Pd(dppf)Cl2 (10 mol %) in THF (5 ml) was added but-3-enylmagnesium bromide (8 ml, 4 mmol, 0.5 M in THF). The solution was then heated at reflux overnight. The solution was cooled down and quenched with ammonia chloride (aq) and filtered through celite. The filtrate was extracted with EtOAc (2×25 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was introduced to a silica gel loading column and purified by column chromatography (20-40% EtOAc/hexanes) to provide the desired product (270 mg, 0.62 mmol), 62%. MS (m/z) 439 [M+H]+. Intermediate I-1A was used in the synthesis of Example 4.

Workup

  1. temperatureThe solution was then heated
  2. temperatureat reflux overnight
  3. temperatureThe solution was cooled down
  4. customquenched with ammonia chloride (aq)
  5. filtrationfiltered through celite
  6. extractionThe filtrate was extracted with EtOAc (2×25 ml)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionThe crude product was introduced to a silica gel loading column
  11. custompurified by column chromatography (20-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f3af99928b1e41a1a076cfaccc586a83
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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