Ethyl Acetate → Tert-butyl 4-(5-acetyl-3-chloropyridin-2-yl)piperazine-1-carboxylate

HRID 730817Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21](=[O:26])N(OC)C)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Mg+].[Br-].[C:30]([O-])(O)=O.[Na+].CCOC(C)=O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21](=[O:26])[CH3:30])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-[3-chloro-5-(methoxy-methyl-carbamoyl)-pyridin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester from step (b) above (1.0 g, 2.6 mmol) in anhydrous THF (20 mL) was added MeMgBr (2.6 mL, 3M solution in Et2O, 7.8 mmol, Aldrich) with stirring at 0° C. The reaction mixture was stirred at room temperature for 4 h and poured into satd. aq. NaHCO3 solution (20 mL). After the addition of EtOAc (50 mL), the mixture was washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (70% EtOAc in hexane) to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 340 (M+1).

Workup

stirringThe reaction mixture was stirred at room temperature for 4 h
additionpoured into satd
washthe mixture was washed with brine (20 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography (70% EtOAc in hexane)

Sources & evidence

ORD record: ord-ec5b8e4605144f82bca94b0529b1f884
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582761B2

Reaction notes

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