Sodium hydride → Tert-butyl 4-(6-cyclobutoxypyrimidin-4-yl)piperazine-1-carboxylate

HRID 1464954Notes

Reaction equation

[H-].[Na+].[CH:3]1([OH:7])[CH2:6][CH2:5][CH2:4]1.Cl[C:9]1[N:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH:10]=1>CN(C=O)C>[CH:3]1([O:7][C:9]2[N:14]=[CH:13][N:12]=[C:11]([N:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH:10]=2)[CH2:6][CH2:5][CH2:4]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of sodium hydride (60% in mineral oil, 469 mg, 11.7 mmol) in DMF (15 mL) was added cyclobutanol (0.92 ml, 11.7 mmol) at 0° C. After stirring at 0° C. for 30 min, a solution of tert-butyl 4-(6-chloropyrimidin-4-yl)piperazine-1-carboxylate (700 mg, 2.34 mmol) in DMF (0.5 mL) was slowly added, and the mixture was stirred at rt for 12 h. Then, the mixture was poured onto water, and the aqueous layer was extracted with EtOAc (twice). The combined organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with hexane/EtOAc (5:1-3:1) to give 687 mg (88% yield) of the title compound as a white solid.

Workup

stirringthe mixture was stirred at rt for 12 h
additionThen, the mixture was poured onto water
extractionthe aqueous layer was extracted with EtOAc (twice)
dry with materialThe combined organic layer was dried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography on silica gel eluting with hexane/EtOAc (5:1-3:1)

Sources & evidence

ORD record: ord-7e75f1c1ea534cc7bfccb30e6bf5a591
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999974B2

Reaction notes

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