Potassium Carbonate → Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

HRID 220543Notes

Reaction equation

Cl[C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(=O)([O-])[O-].[K+].[K+].CN(C)C(=O)C>C(OC)(C)(C)C.O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:2]2[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

Conditions

Temperature: 110 °C

Procedure

Charge a 2 L 3-neck round bottom flask with 2,3-dichloropyrazine (78.7 g, 0.532 mol), piperazine-1-carboxylic acid t-butyl ester (100 g, 0.537 mol), potassium carbonate (88.2 g, 0.638 mol) followed by N,N-dimethylacetamide (0.780 L), and heat the resultant slurry to 110° C. under nitrogen with vigorous stirring. Cool to room temperature, add water (0.390 L) and methyl t-butyl ether (0.390 L), and stir the mixture for 60 min. Stop stirring and separate the layers. Wash the organic layer with water (2×200 mL), dry over MgSO4, filter and concentrate to give 145 g of 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester as a yellow syrup (91% yield). 1H NMR (400 MHz, chloroform-d) δ ppm-8.10 (s, 1H), 7.91 (s, 1H), 3.59 (m, 4H), 3.40 (m, 4H), 1.48 (s, 9H)

Workup

temperatureCool to room temperature
stirringStop stirring
customseparate the layers
washWash the organic layer with water (2×200 mL)
dry with materialdry over MgSO4
filtrationfilter
concentrationconcentrate

Sources & evidence

ORD record: ord-6d8f7ef575774e359391c3e95a341834
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202873B2

Reaction notes

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