4,5-Difluoro-2-methoxyphenylacetic acid → 2-(4,5-Difluoro-2-methoxyphenyl)ethan-1-ol

HRID 921182Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH2:9][C:10](O)=[O:11])=[C:4]([O:13][CH3:14])[CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH2:9][CH2:10][OH:11])=[C:4]([O:13][CH3:14])[CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 2-(4,5-difluoro-2-methoxyphenyl)acetic acid (1 g, 4.95 mmol) in THF (20 mL) at 0° C. was added 1M LAH (9.89 mL, 9.89 mmol) in THF and the resulting mixture was heated at 60° C. for 3 h. Mixture was then cooled and quenched with dropwise addition of water (0.5 mL), 1N NaOH (0.5 mL), and then 1 mL H2O. After stirring for 15 min. the mixture was filtered through celite. The filtrate was concentrated in vacuo. The residue was dried under high vacuum to afford 2-(4,5-difluoro-2-methoxyphenyl)ethanol (800 mg, 4.25 mmol, 86% yield) as a clear viscous oil. Used as is in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ 7.02 (t, J=9.8 Hz, 1H), 6.71 (dd, J=12.1, 6.7 Hz, 1H), 3.87-3.82 (m, 2H), 3.81 (s, 3H), 2.85 (t, J=6.5 Hz, 2H), 1.56 (br. s., 1H).

Workup

temperatureMixture was then cooled
customquenched with dropwise addition of water (0.5 mL), 1N NaOH (0.5 mL)
filtrationwas filtered through celite
concentrationThe filtrate was concentrated in vacuo
customThe residue was dried under high vacuum

Sources & evidence

ORD record: ord-fcff42c4b03e4b57b5e907805e54eff9
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273067B2

Reaction notes

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