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2,3-Difluoro-6-methoxyphenylacetic acid → 2-(2,3-Difluoro-6-methoxyphenyl)ethanol

HRID 921175
Notes
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Reaction equation

HRID 921175 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[CH2:11][C:12](O)=[O:13].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[CH2:11][CH2:12][OH:13]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 38035492,3-Difluoro-6-methoxyphenylacetic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 1172810202-(2,3-Difluoro-6-methoxyphenyl)ethanolYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(2,3-difluoro-6-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-(2,3-difluoro-6-methoxyphenyl)ethanol (810 mg, 4.30 mmol, 87% yield) as a clear viscous oil. Used as is in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ 7.01 (q, J=9.2 Hz, 1H), 6.62-6.53 (m, 1H), 3.92-3.75 (m, 5H), 3.00 (td, J=6.6, 1.9 Hz, 2H), 1.65 (t, J=5.7 Hz, 1H).

Workup

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

Sources & evidence

ORD record
ord-4bb99150f12f44d09de953b43635a720
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09273067B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes