Toluene → Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate
Reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[Li]CCCC.CN([CH:36]=[O:37])C>>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:6]=[CH:7][C:2]([CH:36]=[O:37])=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]Participants
Conditions
- Temperature
- 0 °C
Procedure
To a −78° C. solution of 1-(4-bromophenyl)-4-(tert-butoxycarbonyl)piperazine (9.98 g, 29.2 mmol, prepared as described in Example 1) in TI (70 mL) and toluene (70 mL) was added nBuLi (1.6 M in hexanes, 19 mL, 30.4 mmol) at a rate to maintain an internal temperature below −65° C. The resulting solution was stirred 15 min, then treated with DMF (5 mL). The mixture was stirred 30 min at −78° C., then allowed to warm to 0° C., quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and concentrated. The crude material was crystalized from dichloromethane/ether/hexanes to give 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]benzaldehyde. The filtrates were purified by flash chromatography (30% ethyl acetate/hexanes to 60% ethyl acetate/hexanes) to provide an additional 2.16 g of the desired product.
Workup
- temperatureto maintain an internal temperature below −65° C
- stirringThe mixture was stirred 30 min at −78° C.
- customquenched with saturated ammonium chloride
- extractionextracted with ethyl acetate
- washThe organic phase was washed with brine
- dry with materialdried over MgSO4
- concentrationconcentrated
- customThe crude material was crystalized from dichloromethane/ether/hexanes
Sources & evidence
- ORD record
- ord-cc2f8428675c4e77adeb2372b4524592
- Source dataset
- uspto-grants-2006_03
- Patent number
- US07012075B2
Reaction notes
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