Diisopropylethylamine → 4-Benzyl-1-(4-fluoro-2-methyl-phenyl)-piperazine-2-carboxylic acid ethyl ester

HRID 2065755Notes

Reaction equation

[CH2:1]([NH:8][CH2:9][CH2:10][NH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[CH2:29]([O:31][C:32](=[O:37])[CH:33](Br)[CH2:34]Br)[CH3:30]>C1(C)C=CC=CC=1>[CH2:29]([O:31][C:32]([CH:33]1[CH2:34][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH2:10][N:11]1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[CH3:19])=[O:37])[CH3:30]

Participants

Conditions

Temperature: 135 °C

Procedure

To N-benzyl-N′-(4-fluoro-2-methyl-phenyl)-ethane-1,2-diamine (15.1 g) in toluene (150 mL) was added N,N-diisopropylethylamine (33.8 mL) and 2,3-dibromopropionic acid ethyl ester (25.61 mL) in toluene (350 mL). The reaction mixture was heated to 135° C. for 18 h, cooled to room temperature, and the precipitated solid was removed by filtration. The solution was concentrated, and the crude material was redissolved in TBME and washed with an aqueous 2M solution of Na2CO3 and brine, dried (Na2SO4), filtered and evaporated. Chromatography (SiO2, n-heptane/ethyl acetate 97:3) gave 4-benzyl-1-(4-fluoro-2-methyl-phenyl)-piperazine-2-carboxylic acid ethyl ester (5.5 g) as yellow oil, MS: 357.3 ([M+H]+) and 1-benzyl-4-(4-fluoro-2-methyl-phenyl)-piperazine-2-carboxylic acid ethyl ester (3.3 g) as yellow oil, MS: 357.1 ([M+H]+).

Workup

temperaturecooled to room temperature
customthe precipitated solid was removed by filtration
concentrationThe solution was concentrated
dissolutionthe crude material was redissolved in TBME
washwashed with an aqueous 2M solution of Na2CO3 and brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-b47ca0149a1a4625a22a8d1d0d6712bf
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288541B2

Reaction notes

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