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Acetaldehyde → 2,6-Difluoro-alpha-methyl-3-pyridinemethanol

HRID 16339
Notes
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Reaction equation

HRID 16339 reaction equation
C(NC(C)C)(C)C.CCCCCC.C([Li])CCC.[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[N:21]=1.[CH:27](=[O:29])[CH3:28].Cl>C1(C)C=CC=CC=1.C(OCC)(=O)C.O1CCCC1>[F:19][C:20]1[C:25]([CH:27]([OH:29])[CH3:28])=[CH:24][CH:23]=[C:22]([F:26])[N:21]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 5

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 739342,6-DifluoropyridineHCID 178418244HCID 178418244, compound

Product 1

HCID 220383052,6-Difluoro-alpha-methyl-3-pyridinemethanol

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent
HCID 8028TetrahydrofuranSolvent2×
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-60 °C

Procedure

In nitrogen atmosphere, diisopropylamine (134 mL) was dropwise added to a solution mixture of an n-butyl lithium hexane solution (2.62 M, 368 mL) and tetrahydrofuran (800 mL) at −60° C. or below. The resulting reaction solution was stirred at −60° C. for 30 min, and then a tetrahydrofuran solution (100 mL) of 2,6-difluoropyridine (100 g) was dropwise added thereto at −60° C. or below. The resulting reaction solution was stirred at the same temperature for 1 hr, and then acetoaldehyde (97.6 mL) was dropwise added thereto. Then, a 2 N hydrochloric acid aqueous solution (1000 mL) was dropwise added to the reaction solution, and further ethyl acetate (1000 mL) and toluene (1000 mL) were added thereto. The organic layer was separated and concentrated under reduced pressure to give 129 g of the title compound. The physical property values of this compound were as follows:

Workup

  1. customThe resulting reaction solution
  2. customat −60° C. or below
  3. customThe resulting reaction solution
  4. stirringwas stirred at the same temperature for 1 hr
  5. additionwere added
  6. customThe organic layer was separated
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-491984727908469bba1e13abad271722
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07737141B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes