N,N-Diethylethanamine trihydrofluoride → Ethyl-4,4-difluorocyclohexane carboxylate

HRID 1049322Notes

Reaction equation

HRID 1049322 reaction equation
[FH:1].[FH:2].F.C(N(CC)CC)C.O=[C:12]1[CH2:17][CH2:16][CH:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][CH2:13]1.C([O-])(O)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][C:12]1([F:2])[CH2:17][CH2:16][CH:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 175505N,N-Diethylethanamine trihydrofluorideHCID 317638Ethyl 4-oxocyclohexanecarboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 2779138Ethyl-4,4-difluorocyclohexane carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of triethylamine trihydrofluoride (0.479 mL, 2.94 mmol) in DCE (6 mL) at RT was treated with XtalFluor-M (1.071 g, 4.41 mmol) followed by ethyl 4-oxocyclohexanecarboxylate (0.500 g, 2.94 mmol) and the mixture heated to reflux for 2.5 h. The mixture was cooled to RT, treated with satd. NaHCO3 and stirred overnight. The mixture was diluted with DCM, the layers separated, the aqueous layer extracted with additional DCM (1×) and the combined organics were dried over MgSO4 and filtered through a small pad of silica gel, rinsing well with DCM. The filtrate was concentrated to dryness and purified via silica gel chromatography (DCM/Hex) to afford ethyl 4,4-difluorocyclohexanecarboxylate (390 mg, 69%) as a colorless oil. 1H NMR (400 MHz, DMSO-d6): δ 4.05 (q, J=7.1 Hz, 2H), 2.49 (m, 1H), 2.02-1.77 (m, 6H), 1.65-1.50 (m, 2H), 1.16 (t, J=7.1 Hz, 3H).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 2.5 h
  3. additiontreated with satd
  4. customthe layers separated
  5. extractionthe aqueous layer extracted with additional DCM (1×)
  6. dry with materialthe combined organics were dried over MgSO4
  7. filtrationfiltered through a small pad of silica gel
  8. washrinsing well with DCM
  9. concentrationThe filtrate was concentrated to dryness
  10. custompurified via silica gel chromatography (DCM/Hex)

Sources & evidence

ORD record
ord-9bf573e8f4124a708b4c179f03552441
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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