1-Benzyl-3-bromobenzene → 4-(3'-Benzylphenyl)-3-(S)-iso-propyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 25859

Reaction equation

CC([O-])(C)C.[Na+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][NH:17][C@@H:16]([CH:20]([CH3:22])[CH3:21])[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[CH2:23]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32](Br)[CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(Cl)Cl.CO>C1(C)C=CC=CC=1.CCOCC.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].C1(P(C2C=CC=CC=2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)C=CC=CC=1>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:32]2[CH:33]=[CH:34][CH:35]=[C:30]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:31]=2)[C@@H:16]([CH:20]([CH3:22])[CH3:21])[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

Conditions

Temperature: 80 °C

Procedure

9.4 mg (10.3 μmol, 0.013 eq.) Pd2(dba)3 and 11.4 mg (29.9 μmol, 0.04 eq.) 2-Diphenylphosphino-2′-dimethylamino-biphenyl were dissolved in 6 ml dry toluene. Then 170.7 mg (1.78 mmol, 2.32 eq.) NaOt-Bu was added, followed by a solution of 175.0 mg (0.77 mmol) 3-(S)-Isopropyl-piperazine-1-carboxylic acid tert-butyl ester (85) and 290.6 mg (1.18 μmol, 1.54 eq.) 1-Benzyl-3-bromo-benzene (87). The resulting mixture was heated at 80° C. for 22 h. After cooling to room temperature the mixture was diluted with ether and washed with brine. The comb. org. fractions were dried over Na2SO4 and evaporated. Column chromatography (hexanes/EtOAc (3+1)) yielded 276.5 mg (0.70 mmol, 91.49%) 4-(3′-Benzylphenyl)-3-(S)-iso-propyl-piperazine-1-carboxylic acid tert-butyl ester (88).

Workup

temperatureAfter cooling to room temperature the mixture
washwashed with brine
dry with materialfractions were dried over Na2SO4
customevaporated

Sources & evidence

ORD record: ord-f3e25a85adf64b2aa5d09bac8840401a
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06858600B2

Linked notes

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