1-Methylpiperazine → 1-Methyl-4-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}piperazine
Reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)=[CH:5][CH:4]=1.[CH3:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>ClCCl>[CH3:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:2][C:3]2[CH:8]=[CH:7][C:6]([B:9]3[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]3)=[CH:5][CH:4]=2)[CH2:21][CH2:20]1Participants
Procedure
A solution of 2-(4-Bromomethyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (60 mg, 212 mmol) in N-methyl piperazine (0.5 mL) was heated at 70-75° C. for 3 h. The reaction mixture was cooled down to RT, diluted with dichloromethane (6 mL), washed with water (2×2 mL), brine (2 mL), dried over anhydrous sodium sulphate and concentrated in vacuo to yield 1-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxborolan-2-yl)-benzyl]-piperazine in reasonably good purity. This boronate ester was used for Suzuki coupling reaction with 3-(4-Iodo-benzyl)-5-(R)-phenyl)-oxazolidin-2-one (40 mg, 105 mmol), without any purification, as described in General Procedure (5). The desired product was isolated as a white solid (28 mg, 60%) by silica gel column chromatography. 1H NMR (300 MHz, CDCl3): δ 7.56 (m, 4H), 7.38 (m, 9H), 5.52 (t, 1H), 4.61 (d, 1H), 4.46 (d, 1H), 3.83 (t, 1H), 3.57 (s, 2H), 3.37 (dd, 1H), 2.53 (bs, 8H), 2.32 (s, 3H). (Note: where N-Boc protected piperazine was used as the base, the final product was obtained by cleaving off the Boc group using trifluoro acetic acid in dichloromethane.)
Workup
- washwashed with water (2×2 mL), brine (2 mL)
- dry with materialdried over anhydrous sodium sulphate
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-71cdee80c72a43ef9e629d1d161807ea
- Source dataset
- uspto-grants-2010_10
- Patent number
- US07816354B2
Reaction notes
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