Triethylamine → Ethyl 4-(3-cyano-4-fluorobenzyl)piperazine-1-carboxylate

HRID 1169599Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][C:22]=1[F:23])[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16](C)(C)[CH3:17])=[O:14])[CH2:9][CH2:8]1)#[N:2].CCN(CC)CC.ClC(OCC)=O>C(Cl)Cl.C(O)(C(F)(F)F)=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][C:22]=1[F:23])[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:9][CH2:8]1)#[N:2]

Participants

Conditions

Temperature: 0 °C

Procedure

The tert-butyl 4-(3-cyano-4-fluorobenzyl)piperazine-1-carboxylate from the previous step (15.0 g, 47.0 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (150 mL), to which TFA (150 mL) was slowly added and the resultant mixture stirred for 10 minutes. CH2Cl2 and TFA were removed by concentration in vacuo. The resulting residue was dissolved in THF (170 mL) and Et3N (Aldrich, redistilled, 16.6 mL, 188.1 mmol, 4.0 equiv.). The reaction vessel was cooled to 0° C. and ethyl chloroformate (Aldrich, 4.7 mL, 49.4 mmol, 1.05 equiv.) was added dropwise via syringe under a nitrogen atmosphere. After 30 minutes the reaction was concentrated under reduced pressure, diluted with EtOAc, washed with sat. aq. NaHCO3 and brine, and dried over Na2SO4. The organic layer was removed in vacuo to yield 5.9 g of ethyl 4-(3-cyano-4-fluorobenzyl)piperazine-1-carboxylate.

Workup

additionwas slowly added
customCH2Cl2 and TFA were removed by concentration in vacuo
dissolutionThe resulting residue was dissolved in THF (170 mL)
concentrationAfter 30 minutes the reaction was concentrated under reduced pressure
additiondiluted with EtOAc
washwashed with sat. aq. NaHCO3 and brine
dry with materialdried over Na2SO4
customThe organic layer was removed in vacuo

Sources & evidence

ORD record: ord-d3b359cec49a49838cf7fd2ed837d855
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07825120B2

Reaction notes

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