Dimethylformamide → (6-Phenoxypyridin-3-yl)methanol

HRID 78204Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C([Li])CCC.CN(C)[CH:22]=[O:23].[BH4-].[Na+]>O.CO.C(OCC)C>[O:8]([C:5]1[N:6]=[CH:7][C:2]([CH2:22][OH:23])=[CH:3][CH:4]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a diethyl ether (30.0 mL) solution of 5-bromo-2-phenoxy-pyridine (1.02 g, 4.08 mmol) described in Manufacturing Example 40-1-1 was added dropwise n-butyl lithium (2.55 M n-hexane solution, 1.92 mL, 4.90 mmol) on a dry ice-ethanol bath (−78° C.) under nitrogen atmosphere, which was stirred for 30 minutes at −78° C. Thereafter, N,N-dimethylformamide (378 μL, 4.90 mmol) was added dropwise, which was stirred for 10 minutes at −78° C. Then, sodium borohydride (309 mg, 8.16 mmol) and methanol (15.0 mL) were added, which was stirred for 20 minutes at room temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:1) to obtain the title compound (2.93 g, 66.5%).

Workup

stirringwhich was stirred for 10 minutes at −78° C
stirringwhich was stirred for 20 minutes at room temperature
extractionwas extracted with ethyl acetate
washThe organic layer was washed with saturated aqueous sodium chloride
customthe solvent was evaporated under a reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:1)

Sources & evidence

ORD record: ord-4eafdc39b2be4ec9a65ea82d6fd95256
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841327B2

Reaction notes

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