tert-Butyl mercaptan → HCID 131734345, compound

HRID 1505007Notes

Reaction equation

HRID 1505007 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][CH:6]=[C:5]2[Cl:13].Br[C:15]1[C:16]([F:26])=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[C:18]2[Cl:25].[CH3:27][C:28]([SH:31])([CH3:30])[CH3:29].[Na].C([O-])([O-])=O.[Na+].[Na+].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>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]>[C:28]([S:31][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][CH:6]=[C:5]2[Cl:13])([CH3:30])([CH3:29])[CH3:27].[C:28]([S:31][C:15]1[C:16]([F:26])=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[C:18]2[Cl:25])([CH3:30])([CH3:29])[CH3:27]

Participants

7

Reactant 4

HCID 6387tert-Butyl mercaptanHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 131734344HCID 131734344, compoundHCID 131734346HCID 131734346, compound

Product 1

HCID 131734345HCID 131734345, compoundYield 88.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

A mixture of 6-bromo-4-chloro-7-fluoroquinoline/6-bromo-4-chloro-5-fluoroquinoline (20.35 g, 78 mmol), 2-methylpropane-2-thiol (9.68 ml, 86 mmol), sodium Na2CO3 (24.84 g, 234 mmol), Pd2dba3 (7.15 g, 7.81 mmol), and Xantphos (4.52 g, 7.81 mmol) in 1,4-Dioxane (300 ml) was stirred under nitrogen at 95° C. overnight. Cooled to RT and concentrated. Dissolved resulting material into DCM/water, and separated the layers. Extracted aqueous layer with DCM. The combined organic layers were concentrated. The crude sample was purified via Isco normal phase chromatography (330 g column, 0% -15%, E/H) to yield 6-(tert-butylthio)-4-chloro-7-fluoroquinoline/6-(tert-butylthio)-4-chloro-5-fluoroquinoline (˜20.5 g) as a yellow solid that still contained dba. MS: m/z: 270.0 [M+H]+. This sample was a mixture of regioisomers that was used as is for next step.

Workup

  1. temperatureCooled to RT
  2. concentrationconcentrated
  3. dissolutionDissolved
  4. customresulting material into DCM/water
  5. customseparated the layers
  6. concentrationThe combined organic layers were concentrated
  7. customThe crude sample was purified via Isco normal phase chromatography (330 g column, 0% -15%, E/H)

Sources & evidence

ORD record
ord-cd612527153b45328f6f93d6a66c5aab
Source dataset
uspto-grants-2015_12
Patent number
US09216965B2

Reaction notes

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