Acetone → 2-Bromo-5-fluoro-alpha,alpha-dimethyl-4-pyridinemethanol

To a solution of 2-bromo-5-fluoro-pyridine (CAS 41404-58-4, 25.0 g, 139 mmol) in THF (300 ml) was added dropwise LDA (100 ml of a 2M soln. in THF/heptane/ethylbenzene, 200 mmol) at −78° C. under a N2 atmosphere. Stirring was continued for 1 h at −78° C., then acetone (20.44 ml, 16.17 g, 278 mmol) was added dropwise and stirring was continued at −78° C. for another 1 h. The reaction mixture was quenched with aq. 1M NH4Cl soln. and diluted with EtOAc. The phases were separated and the aq. phase was twice reextracted with EtOAc. The combined org. phases were washed with brine, dried over Na2SO4, filtered, concentrated. Flash chromatography on silica gel (gradient cyclohexane:EtOAc 100:0 to 90:10) followed by crystallization from pentane yielded the title compound as a colourless solid. HPLC RtH4=0.81 min; ESIMS: 234, 236 [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 8.32 (br s, 1H), 7.71 (d, 1H), 5.57 (s, 1H), 4.90 (t, 1H), 3.65-3.57 (m, 1H), 3.53-3.44 (m, 1H), 1.39 (s, 3H).

1. customat −78° C.
2. stirringstirring
3. waitwas continued at −78° C. for another 1 h
4. customThe reaction mixture was quenched with aq. 1M NH4Cl soln
5. additionand diluted with EtOAc
6. customThe phases were separated
7. washphases were washed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customFlash chromatography on silica gel (gradient cyclohexane:EtOAc 100:0 to 90:10) followed by crystallization from pentane

ORDレコード

ord-04029130413c4296943d046dbb9cd382

出典データセット

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08637508B2