Benzyl mercaptan → (Z)-ethyl 3-(2-amino-5-(benzylthio)phenyl)but-2-enoate

HRID 1504413Notes

Reaction equation

HRID 1504413 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][C:3]=1/[C:9](/[CH3:16])=[CH:10]\[C:11]([O:13][CH2:14][CH3:15])=[O:12].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.CCN(C(C)C)C(C)C.[CH2:68]([SH:75])[C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1>O1CCOCC1.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].O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:75][CH2:68][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)=[CH:4][C:3]=1/[C:9](/[CH3:16])=[CH:10]\[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

8

Reactant 4

HCID 7509Benzyl mercaptanHCID 81531Diisopropylethylamine2×HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 117746854(Z)-ethyl 3-(2-amino-5-bromophenyl)but-2-enoate

Product 1

HCID 117746848(Z)-ethyl 3-(2-amino-5-(benzylthio)phenyl)but-2-enoateYield 58%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (Z)-ethyl 3-(2-amino-5-bromophenyl)but-2-enoate (3.3817 g, 11.90 mmol), xantphos (1.033 g, 1.785 mmol), pd2(dba)3 (0.545 g, 0.595 mmol), and n,n-diisopropylethylamine (6.24 ml, 35.7 mmol) in 24 mL dioxane was heated to 80° C. then was treated with benzyl mercaptan (2.252 ml, 19.04 mmol). After stirring for 36 hours, an additional portion of xantphos (1.033 g, 1.785 mmol), pd2(dba)3 (0.545 g, 0.595 mmol), and n,n-diisopropylethylamine (6.24 ml, 35.7 mmol) was added, and the reaction mixture was heated to 90° C. overnight. The reaction mixture was then poured into water and was extracted with DCM. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by silica gel column chromatography (0-100% EtOAc/heptane) gave (Z)-ethyl 3-(2-amino-5-(benzylthio)phenyl)but-2-enoate (2.26 g, 6.90 mmol, 58.0% yield). m/z (ESI) 328.2 (M+H)+.

Workup

  1. extractionwas extracted with DCM
  2. dry with materialThe organics were dried over MgSO4
  3. concentrationconcentrated
  4. customPurification of the crude residue by silica gel column chromatography (0-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-8a63cb9fffce41bab915b596c0f63f95
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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