Lithium Hexamethyldisilazide → 4-(benzyloxy)pyridin-2-amine
Reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11](Cl)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[Li+].C[Si]([N-:55][Si](C)(C)C)(C)C>C1COCC1.Cl.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]>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([NH2:55])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
7
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 50 °C
Procedure
4-(benzyloxy)-2-chloropyridine (18.6 g, 84.7 mmol), XPHOS (4.04 g, 8.47 mmol), and Pd2dba3 (3.88 g, 4.23 mmol) were mixed in THF (250 mL). LHMDS (93.1 ml, 93.1 mmol) was added and the reaction was heated at 50° C. for 1.5 hours. The solution was cooled and diluted with 1N HCl (50 mL) and stirred at ambient temperature for 2 hours. The reaction was concentrated and the residue was extracted with EtOAc. The aqueous layer was basified with saturated K2CO3 and the aqueous layer was extracted with EtOAc. The combined organic layers were dried and concentrated to give the desired product (11.9 g, 70.2% yield) as a brown solid.
Workup
- temperatureThe solution was cooled
- concentrationThe reaction was concentrated
- extractionthe residue was extracted with EtOAc
- extractionthe aqueous layer was extracted with EtOAc
- customThe combined organic layers were dried
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-fa84e86061a148fe8272fc9c06874a48
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08022222B2
Reaction notes
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