Benzylamine → 4-(3-Benzylamino-2-cyano-6-fluoro-phenyl)-piperazine-1-carboxylic Acid Tert-butyl Ester

HRID 459802Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[C:16](F)[C:15]=2[C:22]#[N:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:30]([NH2:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[C:16]([NH:37][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:15]=2[C:22]#[N:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To 655 mg (2.03 mmol) of 4-(2-cyano-3,6-difluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester dissolved in 10 mL DMF was added 560 mg (2 eq., 4.06 mmol) potassium carbonate and 243 μL (1.1 eq., 2.22 mmol) benzylamine. The mixture was heated to 100° C. for 5 days, cooled to room temperature and partitioned between ethyl acetate and water, dried over magnesium sulfate and concentrated. 4-(3-Benzylamino-2-cyano-6-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (288 mg) was precipitated from dichloromethane/hexanes.

Workup

temperaturecooled to room temperature
custompartitioned between ethyl acetate and water
dry with materialdried over magnesium sulfate
concentrationconcentrated
custom4-(3-Benzylamino-2-cyano-6-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (288 mg) was precipitated from dichloromethane/hexanes

Sources & evidence

ORD record: ord-4cf98c1a8fae4c5a9287a973f2e85ef1
Source dataset: uspto-grants-2007_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07196087B2

Reaction notes

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