Tetrahydrofuran → 2-(4-t-Butoxy-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile
Reaction equation
[C:1]([O:5][C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8](F)[C:7]=1[CH3:14])([CH3:4])([CH3:3])[CH3:2].[Li+].C[CH:17]([N-:19]C(C)C)C.[CH2:23]1[CH2:27]O[CH2:25][CH2:24]1>>[C:1]([O:5][C:6]1[C:11]([F:12])=[CH:10][N:9]=[C:8]([CH:24]2[CH2:25][CH:23]2[CH2:27][C:17]#[N:19])[C:7]=1[CH3:14])([CH3:4])([CH3:3])[CH3:2]Participants
Conditions
- Temperature
- -78 °C
Procedure
A sample of 4-t-butoxy-2,5-difluoro-3-methylpyridine (40.8 mmol) was dissolved in 50 mL of THF and cooled to -78° C. To this was added a freshly prepared solution of LDA (0.103 mmol) in 50 mL of THF at -78° C,, and the reaction was stirred for 1 hour. The reaction was then stirred at 0° C. for 1 hour, quenched with saturated NH4Cl solution and extracted with ether. The extracts were washed with saturated NaCl solution, dried over MgSO4, and concentrated. The residue was purified by flash chromatography, eluting with 1:4 ethyl acetate:hexane, to yield 10.33 g of 2-(4-t-butoxy-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile after removal of the solvent. MS 263 (M+H)+ ; 1H NMR (CDCl3)∂: 0.50 (m, 2H), 0.63 (m, 1H), .73 (m, 1H), 1.60 (m, 1H), 1.43 (d, 9H, J=2 Hz), 2.29 (s, 3H), 3.76 (d, 1H, J=8 Hz), 8.30 (d, 1H, J=3 Hz). IR (neat) 2240, 1580, 1470 cm-l.
Workup
- stirringThe reaction was then stirred at 0° C. for 1 hour
- customquenched with saturated NH4Cl solution
- extractionextracted with ether
- washThe extracts were washed with saturated NaCl solution
- dry with materialdried over MgSO4
- concentrationconcentrated
- customThe residue was purified by flash chromatography
- washeluting with 1:4 ethyl acetate
Sources & evidence
- ORD record
- ord-ecb4189b2c484cd3a727d679046b64d3
- Source dataset
- uspto-grants-1999_11
- Patent number
- US05977133
Reaction notes
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