Ethyl 3-bromobenzoate → 3-(4-(Tert-butoxycarbonyl)piperazin-1-yl)benzoic acid
Reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7]CC)=[O:6].[N:13]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.CC([O-])(C)C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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]>[C:22]([O:21][C:19]([N:13]1[CH2:18][CH2:17][N:16]([C:2]2[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=2)[C:5]([OH:7])=[O:6])[CH2:15][CH2:14]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 110 °C
Procedure
The mixture of ethyl 3-bromobenzoate (500 mg, 2.33 mmol), tert-butyl piperazine-1-carboxylate (433 mg, 2.33 mmol) and NaOtBu (268 mg, 2.78 mmol), Pd2(dba)3 (20 mg, 0.034 mmol) and Xantphos (20 mg, 0,034 mmol) in anhydrous dioxane (10 mL) was heated to 110° C. for 10 h. The mixture was concentrated and the residue was partitioned in water, the solution was adjusted to pH=5, and extracted with DCM. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to afford the title compound that was used for next step (300 mg, Yield 42.2%). LCMS (m/z): 307.1 (M+1).
Workup
- concentrationThe mixture was concentrated
- customthe residue was partitioned in water
- extractionextracted with DCM
- washThe organic layer was washed with water and brine
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-9fd552b8445747d0afc4372a39964a25
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09365519B2
Reaction notes
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