Hydrochloric Acid → 2-ethyl-2-(hydroxymethyl)hexanoic Acid

HRID 916281Notes

Reaction equation

HRID 916281 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH2:13]([CH:15]([CH2:19][CH2:20][CH2:21][CH3:22])[C:16]([OH:18])=[O:17])[CH3:14].[CH2:23]=[O:24].[Cl-].[NH4+].Cl>C1COCC1>[CH2:13]([C:15]([CH2:23][OH:24])([CH2:19][CH2:20][CH2:21][CH3:22])[C:16]([OH:18])=[O:17])[CH3:14]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 7912DiisopropylamineHCID 86972-Ethylhexanoic AcidHCID 25517Ammonium ChlorideHCID 178418339Butyllithium

Product 1

HCID 97939872-ethyl-2-(hydroxymethyl)hexanoic Acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

27 ml (72.9 mmol) of n-butyllithium (2.7 M in heptane) are added dropwise at 0° C. to a solution of 10.9 ml of diisopropylamine (77.5 mmol) in 60 ml of THF, and the mixture is stirred at 0° C. for 30 min. Within 10 min, 5 g (34.7 mmol) of 2-ethylhexanoic acid are added dropwise at 0° C. and the reaction mixture is heated at 50° C. for 1.5 h. The clear solution is cooled to −20° C. and admixed with 3.1 g (103 mmol) of paraformaldehyde. After 10 min at −20° C., the mixture is stirred at RT for 2 h. The mixture is admixed with saturated aqueous solution of ammonium chloride and adjusted to pH=1-2 with 6N HCl. The organic phase is removed, the aqueous phase is re-extracted once with MTBE and the combined organic phases are concentrated on a rotary evaporator. The crude product (85% yield (GC)) can be purified further by distillation (b.p.: 121° C., 0.2 mbar). Alternatively, it is also possible to crystallize the sodium salt of the product from aqueous solution in pure form. The pure product of the free 2-ethyl-2-hydroxymethylhexanoic acid, which is typically obtained as a viscous oil, crystallizes slowly at RT (melting point: 45-46° C.). Alternatively, the product can also be crystallized from a suitable solvent, for example pentane, hexane, heptane or petroleum ether.

Workup

  1. waitWithin 10 min
  2. temperaturethe reaction mixture is heated at 50° C. for 1.5 h
  3. temperatureThe clear solution is cooled to −20° C.
  4. waitAfter 10 min at −20° C.
  5. stirringthe mixture is stirred at RT for 2 h
  6. customThe organic phase is removed
  7. extractionthe aqueous phase is re-extracted once with MTBE
  8. concentrationthe combined organic phases are concentrated on a rotary evaporator
  9. distillationThe crude product (85% yield (GC)) can be purified further by distillation (b.p.: 121° C., 0.2 mbar)
  10. customto crystallize the sodium salt of the product from aqueous solution in pure form

Sources & evidence

ORD record
ord-6f2d57e137ab45e484fc2de17d6aad7a
Source dataset
uspto-grants-2007_09
Patent number
US07268253B2

Reaction notes

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