Pyridine → 8-Hydroxy-8-(6-methoxy-3-pyridyl)-1,4-dioxaspiro[4.5]decane
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[Li]CCCC.N1C=CC=CC=1.[CH2:21]1[O:31][C:24]2([CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]2)[O:23][CH2:22]1>C1COCC1.CO.C(Cl)Cl>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([C:27]2([OH:30])[CH2:28][CH2:29][C:24]3([O:31][CH2:21][CH2:22][O:23]3)[CH2:25][CH2:26]2)=[CH:3][CH:4]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -78 °C
Procedure
In a dried 3-neck flask, 5-bromo-2-methoxypyridine (12.6 g, 67.2 mmol) was dissolved in dry THF (130 mL) and cooled to −78° C. under N2. 2.5M n-BuLi in hexanes (28.2 mL, 70.4 mmol) was added dropwise and the mixture stirred at −78° C. for 50 min. To pyridine mixture was slowly added a solution of 1,4-cyclohexanedione mono-ethylene ketal (10.0 g, 64.0 mmol) in dry THF (25 mL). The resulting mixture was stirred at −78° C. for 80 min. The reaction was quenched with sat'd NH4Cl and extracted with CH2Cl2 (3×). The combined extracts were dried (MgSO4), filtered, and concentrated to give a yellow oil. Flash chromatography on silica gel eluting with 10% MeOH/CH2Cl2 afforded the title compound as a yellow solid; yield 16.5 g, 62.2 mmol, 97%; 1H NMR (CDCl3) δ 8.26 (s, 1H), 7.72 (d, 1H), 6.69 (d, 1H), 3.96 (t, 4H), 3.91 (s, 3H), 2.21 (s, 1H), 2.08 (m, 4H), 1.82 (m, 2H), 1.66 (m, 2H); MS m/z/z=266.1 (M+H)+.
Workup
- stirringThe resulting mixture was stirred at −78° C. for 80 min
- customThe reaction was quenched with sat'd NH4Cl
- extractionextracted with CH2Cl2 (3×)
- dry with materialThe combined extracts were dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated
- customto give a yellow oil
Sources & evidence
- ORD record
- ord-0ee53bf5880e4fa7a26aa1464cc0ef99
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08362003B2
Reaction notes
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