(R)-3-Methylmorpholine → HCID 86699725, compound

HRID 515147Notes

Reaction equation

HRID 515147 reaction equation
Cl[C:2]1[CH:9]=[C:8]([CH3:10])[C:5]([C:6]#[N:7])=[C:4]([S:11][CH2:12][CH3:13])[CH:3]=1.[CH3:14][C@@H:15]1[CH2:20][O:19][CH2:18][CH2:17][NH:16]1.CC(C)([O-])C.[Na+].CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C>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].O1CCOCC1>[CH2:12]([S:11][C:4]1[CH:3]=[C:2]([N:16]2[CH2:17][CH2:18][O:19][CH2:20][C@H:15]2[CH3:14])[CH:9]=[C:8]([CH3:10])[C:5]=1[C:6]#[N:7])[CH3:13]

Participants

7

Reactant 4

HCID 641498(R)-3-MethylmorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86699722HCID 86699722, compound

Product 1

HCID 86699725HCID 86699725, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-Chloro-2-ethylsulfanyl-6-methyl-benzonitrile (synthesized according to the method described in section a) of example 2) (0.20 g, 0.95 mmol), (R)-3-methylmorpholine (0.14 g, 1.42 mmol) and sodium tert-butoxide (0.27 g, 2.85 mmol) are mixed together with dioxane (1 ml) in a microwave vial. The resulting mixture is degassed and flushed with argon for 20 min followed by the addition of (2-biphenyl)di-tert-butylphosphine (0.056 g, 0.19 mmol) and bis(dibenzylideneacetone)-palladium(0) (0.11 g, 0.19 mmol). The reaction mixture is heated at 100° C. in a microwave oven for 1 h. After completion of the reaction (monitored by TLC), the mixture is filtered through a pad of celite and the filtrate is concentrated to get the crude product, which is purified by column chromatography (silica gel, 8% acetone/hexane) to yield 2-ethylsulfanyl-6-methyl-4-[(3R)-3-methyl-morpholin-4-yl]-benzonitrile (0.06 g, 0.217 mmol, 22%).

Workup

  1. customThe resulting mixture is degassed
  2. customflushed with argon for 20 min
  3. customAfter completion of the reaction (monitored by TLC)
  4. filtrationthe mixture is filtered through a pad of celite
  5. concentrationthe filtrate is concentrated
  6. customto get the crude product, which
  7. customis purified by column chromatography (silica gel, 8% acetone/hexane)

Sources & evidence

ORD record
ord-037a5376079b4296b5152f1412deff4b
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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