Valproic Acid → 2-Methyl-2-n-propylpentanoic acid

HRID 1957573Notes

Reaction equation

HRID 1957573 reaction equation
[CH2:1]([Li])CCC.[C:6]([OH:15])(=[O:14])[CH:7]([CH2:11][CH2:12][CH3:13])[CH2:8][CH2:9][CH3:10].CI>CCCCCC>[CH3:1][C:7]([CH2:11][CH2:12][CH3:13])([CH2:8][CH2:9][CH3:10])[C:6]([OH:15])=[O:14]

Participants

5

Reactant 3

HCID 3121Valproic AcidHCID 6328Methyl iodideHCID 178418339Butyllithium2×

Product 1

HCID 1349472-Methyl-2-n-propylpentanoic acid

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

The alkylation of the carboxylic acids at position 2 using alkyl halides is very generally possible with the aid of n-butyllithium at elevated temperature (Pfeffer et al., Alpha-anions of carboxylic acids. II. The formation and alkylation of alpha-metalated aliphatic acids. Journal of Organic Chemistry 37, 451-458 (1972). The methylation of the tertiary carbon atom of valproic acid is possible, for example, by deprotonation of the α-hydrogen atom at C-2 using n-butyllithium in hexane at 50° C. and subsequent methylation with methyl iodide at room temperature in a yield of 32%. The other 2-alkylated carboxylic acids can also be prepared in accordance with this method.

Workup

  1. customat 50° C.
  2. customat room temperature

Sources & evidence

ORD record
ord-d4509c8b12e24f2da210cfee9000c54d
Source dataset
uspto-grants-1998_07
Patent number
US05786380

Reaction notes

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