Morpholine → 2-Ethylsulfanyl-6-methyl-4-morpholin-4-yl-benzonitrile

HRID 515141Notes

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

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-chloro-2-ethylsulfanyl-6-methyl-benzonitrile (0.9 g, 4.26 mmol) in dioxane (90 ml) are added morpholine (0.56 g, 6.39 mmol) and sodium tert-butoxide (1.2 g, 12.8 mmol). The reaction mixture is degassed and flushed with Argon for 30 min and then (2-biphenyl)di-tert-butylphosphine (0.25 g, 0.85 mmol) and bis(dibenzylideneacetone)-palladium(0) (0.5 g, 0.85 mmol) are added. The reaction mixture is stirred at 100° C. for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture is filtered through a pad of celite pad. The filtrate is concentrated to get the crude product, which is purified by column chromatography (silica gel, 5% acetone/hexane) to yield 2-ethylsulfanyl-6-methyl-4-morpholin-4-yl-benzonitrile (0.30 g, 1.14 mmol, 27%).

Workup

customThe reaction mixture is degassed
customflushed with Argon for 30 min
customAfter completion of the reaction (monitored by TLC)
filtrationthe reaction mixture is filtered through a pad of celite pad
concentrationThe filtrate is concentrated
customto get the crude product, which
customis purified by column chromatography (silica gel, 5% acetone/hexane)

Sources & evidence

ORD record: ord-8c23fc8a8e4d4dac95205289021f4a47
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108936B2

Reaction notes

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