Cesium carbonate → tert-Butyl 4-(4-methylpyrimidin-2-yl)piperazine-1-carboxylate

HRID 1775323Notes

Reaction equation

C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:54]1[N:59]=[C:58]([CH3:60])[CH:57]=[CH:56][N:55]=1.[N:61]1([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:60][C:58]1[CH:57]=[CH:56][N:55]=[C:54]([N:64]2[CH2:63][CH2:62][N:61]([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[CH2:66][CH2:65]2)[N:59]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Palladium acetate (45 mg, 0.2 mmol), BINAP (62 mg, 0.1 mmol) and cesium carbonate (650 mg, 2 mmol) were suspended in anhydrous 1,4-dioxane (3 ml) under an argon atmosphere and sonicated for 45 minutes. 2-Bromo-4-methylpyrimidine (173 mg, 1 mmol) and tert-butyl piperazine-1-carboxylate (208 mg, 1.3 mmol) were dissolved in 3 ml anhydrous 1,4-dioxane and the resulting solution was added to the catalyst-containing mixture. The resulting mixture was stirred at 110° C. overnight, afterwards diluted with ethyl acetate and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was purified by column chromatography (silica, gradient from DCM to DCM/ethyl acetate 8/2) to yield 120 mg of a brown oil (0.43 mmol, 43%) MS (APCI) m/z=279.2 [M+1]+.

Workup

customsonicated for 45 minutes
additionthe resulting solution was added to the catalyst-containing mixture
filtrationfiltered
customThe filtrate was evaporated to dryness under reduced pressure
customthe residue was purified by column chromatography (silica, gradient from DCM to DCM/ethyl acetate 8/2)

Sources & evidence

ORD record: ord-82f3a3fd62de4975b120aaea7268aa24
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260441B2

Reaction notes

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