Toluene → 4-(3-Nitro-5-thiomorpholinopyridin-2-yl)morpholine

HRID 1431258Notes

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.C1(C)C=CC=CC=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.[K+].[NH:64]1[CH2:69][CH2:68][S:67][CH2:66][CH2:65]1>CCOC(C)=O.O.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]>[N+:14]([C:4]1[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=[C:2]([N:64]2[CH2:69][CH2:68][S:67][CH2:66][CH2:65]2)[CH:3]=1)([O-:16])=[O:15]

Participants

Conditions

Temperature: 115 °C

Procedure

A stirred solution of 4-(5-chloro-3-nitropyridin-2-yl)morpholine (400 mg, 1.64 mmol) in toluene (15.7 mL, 147.7 mmol) was treated with Pd2dba3 (75 mg, 0.082 mmol), X-Phos (78 mg, 0.16 mmol), potassium tert butoxide (368 mg, 3.28 mmol) and thiomorpholine (203 mg, 1.97 mmol). The reaction was heated at 115° C. overnight. After this time the reaction was cooled to rt and diluted with EtOAc (100 mL) and water (50 mL). The separated organic layer was washed with NaHCO3 (satd aq. solution, 40 mL), brine (40 mL) and then dried over magnesium sulfate, filtered and evaporated in vacuo. Column chromatography (hexanes:EtOAc, 1:0 to 1:2) gave 4-(3-nitro-5-thiomorpholinopyridin-2-yl)morpholine as a red oil. Mass Spectrum (ESI) m/e=311.2 (M+1).

Workup

temperatureAfter this time the reaction was cooled to rt
washThe separated organic layer was washed with NaHCO3 (satd aq. solution, 40 mL), brine (40 mL)
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated in vacuo

Sources & evidence

ORD record: ord-83602b98774c44c5ad10d40c24bdc3f3
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

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