2-(Di-tert-butylphosphino)biphenyl → Methyl-[1-(2-thiophen-3-yl-pyridin-4-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester
Reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:12]=[CH:11][S:10][CH:9]=2)[CH:3]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[C:34]([O:38][C:39](=[O:47])[N:40]([CH3:46])[CH:41]1[CH2:45][CH2:44][NH:43][CH2:42]1)([CH3:37])([CH3:36])[CH3:35].CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[C:34]([O:38][C:39](=[O:47])[N:40]([CH3:46])[CH:41]1[CH2:45][CH2:44][N:43]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]3[CH:12]=[CH:11][S:10][CH:9]=3)[CH:3]=2)[CH2:42]1)([CH3:37])([CH3:36])[CH3:35]Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 90 °C
Procedure
To a solution of 4-chloro-2-thiophen-3-yl-pyridine (50 mg, 0.4 mmol) in toluene (1 mL) was added Pd(OAc)2 (2.3 mg, 0.01 mmol), 2-(di-t-butyl-phosphino)biphenyl (6.0 mg, 0.02 mmol), methyl-pyrrolidin-3-yl-carbamic acid tert-butyl ester (60 mg, 0.45 mmol), and NaOtBu (75 mg, 0.8 mmol). The resulting mixture was stirred at 90° C. for 16 h, then was cooled, poured into water, and extracted with EtOAc. The organic layer was dried and concentrated, and the resulting residue was purified by preparative TLC (hexanes/EtOAc) to yield methyl-[1-(2-thiophen-3-yl-pyridin-4-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a white solid (60 mg, 42%).
Workup
- temperaturewas cooled
- extractionextracted with EtOAc
- customThe organic layer was dried
- concentrationconcentrated
- customthe resulting residue was purified by preparative TLC (hexanes/EtOAc)
Sources & evidence
- ORD record
- ord-2087b8c7bc5c4fbb960389f4acd69d8f
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08022209B2
Reaction notes
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