tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-[2-cyano-4-(trifluoromethyl)phenyl]piperazine-1-carboxylate

HRID 1667536Notes

Reaction equation

[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:15]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:16]=1[C:17]#[N:18].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][N:11]([C:15]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:16]=2[C:17]#[N:18])[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of Boc-piperazine (573 mg, (3.08 mmol), 2-bromo-5-trifluoromethylbenzonitrile (700 mg, 2.80 mmol), Pd2(dba)3 (256 mg, 0.28 mmol), xantphos (486 mg, 0.84 mmol), sodium t-butoxide (660 mg, 7.0 mmol) in degassed anhydrous dioxane (10 mL) was heated at 85° C. for 1 h. The mixture was allowed to cool and filtered through celite. The filtrate was concentrated and purified by chromatography (EtOAc/hexanes) to yield the title compound (150 mg, 15%). m/z (M+1) 356.37.

Workup

temperatureto cool
filtrationfiltered through celite
concentrationThe filtrate was concentrated
custompurified by chromatography (EtOAc/hexanes)

Sources & evidence

ORD record: ord-8f465d2d526846c6bb87d53fb61fc54d
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044041B2

Reaction notes

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