Hydrochloric Acid → 4,4-Difluorocyclohexanecarboxylic acid

HRID 1049323Notes

Reaction equation

HRID 1049323 reaction equation
[F:1][C:2]1([F:13])[CH2:7][CH2:6][CH:5]([C:8]([O:10]CC)=[O:9])[CH2:4][CH2:3]1.O.O.[OH-].[Li+].Cl>C1COCC1.CCOC(C)=O>[F:1][C:2]1([F:13])[CH2:3][CH2:4][CH:5]([C:8]([OH:10])=[O:9])[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 2779138Ethyl-4,4-difluorocyclohexane carboxylate

Product 1

HCID 27791364,4-Difluorocyclohexanecarboxylic acidYield 97%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 4,4-difluorocyclohexanecarboxylate (0.385 g, 2.003 mmol) in THF (12 mL) was treated with H2O (6 mL) followed by lithium hydroxide monohydrate (0.420 g, 10.02 mmol) and the mixture stirred vigorously at RT overnight. The mixture was treated with EtOAc, acidified with 1M HCl until pH 4, the layers separated and the aqueous layer extracted with additional EtOAc (1×). The combined organics were washed with brine, dried over MgSO4 and concentrated to dryness to afford 4,4-difluorocyclohexanecarboxylic acid (318 mg, 97%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 12.28 (s, 1H), 2.40 (m, 1H), 2.02-1.75 (m, 6H), 1.59 (m, 2H).

Workup

  1. customthe layers separated
  2. extractionthe aqueous layer extracted with additional EtOAc (1×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-2560dafa427847c690cdf0dc8311717a
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

Loading…