Toluene → 4-[5-(1,1-Dioxidothiomorpholin-4-yl)-3-nitropyridin-2-yl]morpholine

HRID 1431261Notes

Reaction equation

HRID 1431261 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N+:14]([O-:16])=[O:15])[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[NH:17]1[CH2:22][CH2:21][S:20](=[O:24])(=[O:23])[CH2:19][CH2:18]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+].C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:23]=[S:20]1(=[O:24])[CH2:21][CH2:22][N:17]([C:2]2[CH:3]=[C:4]([N+:14]([O-:16])=[O:15])[C:5]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[N:6][CH:7]=2)[CH2:18][CH2:19]1

Participants

7

Reactant 5

HCID 1140TolueneHCID 6484228Thiomorpholine 1,1-dioxideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596312064-(5-Chloro-3-nitropyridin-2-yl)morpholine

Product 1

HCID 596313874-[5-(1,1-Dioxidothiomorpholin-4-yl)-3-nitropyridin-2-yl]morpholine

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A stirred solution of 4-(5-chloro-3-nitropyridin-2-yl)morpholine (500 mg, 2.05 mmol), thiomorpholine 1,1-dioxide (333 mg, 2.46 mmol), Pd2dba3 (94 mg, 0.10 mmol), X-Phos (98 mg, 0.20 mmol), sodium tert-butoxide (394 mg, 4.1 mmol) in toluene (19.7 mL, 184.7 mmol) was heated at reflux for 14 h. After this time the reaction was cooled to rt and partitioned between EtOAc (100 mL) and NaHCO3 (satd aq. solution, 50 mL). The separated organic layer was washed with brine (50 mL), dried over magnesium sulfate, filtered and evaporated in vacuo. Column chromatography (hexanes:EtOAc, 1:0 to 1:1) gave 4-[5-(1,1-dioxidothiomorpholin-4-yl)-3-nitropyridin-2-yl]morpholine.

Workup

  1. temperatureat reflux for 14 h
  2. custompartitioned between EtOAc (100 mL) and NaHCO3 (satd aq. solution, 50 mL)
  3. washThe separated organic layer was washed with brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-845f7dfe42174b5dbd81a64dd0442b68
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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