Ethylene Glycol → tert-butyl (3R)-4-[3-(2-hydroxyethoxy)pyrazin-2-yl]-3-methylpiperazine-1-carboxylate

HRID 1295727Notes

Reaction equation

Cl[C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@H:9]2[CH3:21])=[N:4][CH:5]=[CH:6][N:7]=1.[CH2:22]([OH:25])[CH2:23][OH:24].CC([O-])(C)C.[K+]>CS(C)=O>[OH:24][CH2:23][CH2:22][O:25][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@H:9]2[CH3:21])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of tert-butyl (3R)-4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate* (35 g, 0.11 mol), ethylene glycol (100 g, 1.61 mol) and t-BuOK (25 g, 0.22 mol) in DMSO (150 g) was stirred at 50° C. for 3 h. After this time, the reaction mixture was partitioned between EtOAc (500 g) and water (500 g) and sodium chloride (20 g) was added. The organic layer was concentrated in vacuo to furnish 32.5 g (87%) of the title product. HPLC purity: 75%. HRMS m/z calcd for C16H26N4O4 (M)+ 338.1954, found 338.1959. *Described in WO 00/76984, Example 172, Step 2.

Workup

customAfter this time, the reaction mixture was partitioned between EtOAc (500 g) and water (500 g) and sodium chloride (20 g)
additionwas added
concentrationThe organic layer was concentrated in vacuo

Sources & evidence

ORD record: ord-0e0738a5d6b84072a849fcf60a9332a9
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07244722B2

Reaction notes

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