Benzyl mercaptan → (E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

HRID 1504400Notes

Reaction equation

HRID 1504400 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][C:3]=1/[CH:9]=[CH:10]/[C:11]([O:13][CH2:14][CH3:15])=[O:12].O1CCOCC1.CCN(C(C)C)C(C)C.[CH2:31]([SH:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:38][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:4][C:3]=1/[CH:9]=[CH:10]/[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

8

Reactant 4

HCID 7509Benzyl mercaptanHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 86278419(E)-ethyl 3-(2-amino-5-bromophenyl)acrylate

Product 1

HCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylateYield 122.4%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A screw cap vial was charged with (E)-ethyl 3-(2-amino-5-bromophenyl)acrylate (0.820 g, 2.086 mmol), xantphos (0.092 g, 0.159 mmol), tris(dibenzylideneacetone)dipalladium (0.073 g, 0.080 mmol), 1,4-Dioxane (3.18 ml), and DIPEA (1.108 ml, 6.37 mmol). The vial was purged with Argon, sealed and heated to 80° C. for 10 minutes. The reaction was cooled to RT and benzyl mercaptan (0.395 ml, 3.34 mmol) was added and the reaction was continued heating at 80° C. for an additional 30 minutes. The reaction was cooled to RT, diluted with water and extracted with DCM (3×). The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The resulting material was concentrated, dissolved in minimal DCM and purified via column chromatography (silica gel 40 g, gradient elution 0 to 50% EtOAc:Heptane) to afford 0.80 g of (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate. m/z (ESI) 314.1 (M+H)+.

Workup

  1. customA screw cap vial
  2. customThe vial was purged with Argon
  3. customsealed
  4. temperatureThe reaction was cooled to RT
  5. temperaturethe reaction was continued heating at 80° C. for an additional 30 minutes
  6. temperatureThe reaction was cooled to RT
  7. extractionextracted with DCM (3×)
  8. washThe combined organics were washed with water and brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. concentrationThe resulting material was concentrated
  13. dissolutiondissolved in minimal DCM
  14. custompurified via column chromatography (silica gel 40 g, gradient elution 0 to 50% EtOAc:Heptane)

Sources & evidence

ORD record
ord-76a634c68842473f9658c49982010e00
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

Loading…