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4-Methoxy-alpha-toluenethiol → HCID 89704803, compound

HRID 928991
Notes
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Reaction equation

HRID 928991 reaction equation
Br[C:2]1[C:3]([F:21])=[C:4]([F:20])[C:5]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C(N(CC)C(C)C)(C)C.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.[CH3:73][O:74][C:75]1[CH:80]=[CH:79][C:78]([CH2:81][SH:82])=[CH:77][CH:76]=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]>[F:20][C:4]1[C:5]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[C:6]([CH:11]=[C:2]([S:82][CH2:81][C:78]2[CH:79]=[CH:80][C:75]([O:74][CH3:73])=[CH:76][CH:77]=2)[C:3]=1[F:21])[C:7]([O:9][CH3:10])=[O:8]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 804074-Methoxy-alpha-toluenethiolHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59519391Methyl 5-bromo-2-(2-fluorophenylamino)-3,4-difluorobenzoate

Product 1

HCID 89704803HCID 89704803, compoundYield 90.6%

Reagents, catalysts & solvents

2
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 5-bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoate (22.33 g, 62.01 mmol) in anhydrous 1,4-dioxane (200 mL) was added N,N-diisopropylethylamine (16.03 g, 124.04 mmol). Then Pd2(dba)3 (2.84 g, 3.10 mmol) followed by Xantphos (3.59 g, 6.20 mmol) and 4-methoxy-α-toluenethiol (10.27 g, 65.11 mmol) was added under nitrogen atmosphere. The mixture was stirred overnight at 100° C. under N2 atmosphere and then allowed to warm to ambient temperature. The insoluble matter was filtered off and the filter cake was washed ethyl acetate. The filtrate was diluted with water (300 mL) and extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with water (100 mL) and brine (100 mL) sequentially, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1, v/v) to give the desired product (pale yellow solid, 24.35 g, 90.6% yield). 1H NMR (400 MHz, CDCl3): δ 9.12 (s, 1H), 7.78 (d, 1H), 7.25 (m, 6H), 6.85 (m, 2H), 4.03 (s, 2H), 3.90 (s, 3H), 3.80 (s, 3H).

Workup

  1. additionwas added under nitrogen atmosphere
  2. temperatureto warm to ambient temperature
  3. filtrationThe insoluble matter was filtered off
  4. washthe filter cake was washed ethyl acetate
  5. additionThe filtrate was diluted with water (300 mL)
  6. extractionextracted with ethyl acetate (100 mL×3)
  7. washThe combined organic layers were washed with water (100 mL) and brine (100 mL) sequentially
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1, v/v)

Sources & evidence

ORD record
ord-bef44b0aac0a4ff9baaca7e2df10b453
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09290468B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes