Acetic Acid → ethyl 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)benzoate
Reaction equation
[C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:15][C@H:16]1[NH:21][C@@H:20]([CH3:22])[CH2:19][N:18]([C:23]2[CH:33]=[CH:32][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:25][CH:24]=2)[CH2:17]1.C(O)(=O)C>CO>[CH3:22][C@H:20]1[N:21]([CH3:1])[C@@H:16]([CH3:15])[CH2:17][N:18]([C:23]2[CH:33]=[CH:32][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:25][CH:24]=2)[CH2:19]1Participants
Procedure
Sodium triacetoxyborohydride (5.30 g, 25.00 mmol) was added to ethyl 4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzoate (2.62 g, 10 mmol), and acetic acid (1.145 mL, 20.00 mmol) in methanol (15 mL) at 25° C. The resulting solution was stirred at ambient temperature for 18 h. The reaction mixture was quenched with saturated NaHCO3 (15 mL) to pH7 and the crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford an oil. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)benzoate (1.960 g, 70.9%) as a yellow oil. MS: m/z 277 (MH+).
Workup
- customThe reaction mixture was quenched with saturated NaHCO3 (15 mL) to pH7
- customthe crude product was purified by ion exchange chromatography
- washThe desired product was eluted from the column
- customevaporated to dryness
- customto afford an oil
- customThe crude product was purified by silica column chromatography
- washeluting with a gradient of 0 to 5% MeOH in DCM
- customPure fractions were evaporated to dryness
Sources & evidence
- ORD record
- ord-14129e90488a4eb3a445f084229fe3e7
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08604022B2
Reaction notes
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