Methyl 3-mercaptopropionate → HCID 86641275, compound

HRID 578792Notes

Reaction equation

HRID 578792 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:8]=1)[NH2:7].[SH:10][CH2:11][CH2:12][C:13]([O:15]C)=O.C(N(CC)C(C)C)(C)C.[O:26]1CCOC[CH2:27]1>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[F:9][C:5]1[CH:4]=[CH:3][C:2]([S:10][CH2:11][C:12](=[C:13]=[O:15])[O:26][CH3:27])=[CH:8][C:6]=1[NH2:7]

Participants

7

Reactant 4

HCID 18050Methyl 3-mercaptopropionateHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 27694075-Bromo-2-fluoroaniline

Product 1

HCID 86641275HCID 86641275, compound

Reagents, catalysts & solvents 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalyst

Procedure

To a mixture of 5-bromo-2-fluoroaniline (4.15 g), methyl 3-mercaptopropionate (2.62 g), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene (0.63 g) and N,N-diisopropylethylamine (5.64 g) in 1,4-dioxane (80 mL) was added tris (dibenzylidene -acetone) dipalladium(0) (0.3 g), and the mixture was heated for reflux under an argon atmosphere overnight. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1−5/1−2/1) to give 2-fluoro-5-(2-methoxy -carbonylethylthio)aniline (4.62 g). This material was dissolved in tetrahydrofuran (120 mL). To the solution was added potassium tert-butoxide (1 mol/L tetrahydrofuran solution, 80.6 mL) at −78° C., and the mixture was stirred at the same temperature for 15 minutes. To the reaction mixture was added 1 mol/L hydrochloric acid (81 mL), and the mixture was warmed to room temperature and stirred for 5 minutes. The mixture was poured into ethyl acetate, and the organic layer was separated. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1) to give the title compound (1.85 g).

Workup

  1. temperaturethe mixture was heated
  2. temperaturefor reflux under an argon atmosphere overnight
  3. customThe insoluble material was removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1−5/1−2/1)

Sources & evidence

ORD record
ord-1581e32b29e64a48888c8c0f5560a765
Source dataset
uspto-grants-2015_05
Patent number
US09040693B2

Reaction notes

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