N,N-Diethylethanamine trihydrofluoride → HCID 86716176, compound

HRID 512153Notes

Reaction equation

HRID 512153 reaction equation
F[B-](F)(F)F.C(N([S+](F)F)CC)C.[Cl:14][C:15]1[N:20]=[CH:19][C:18]([C:21]2([C:28]#[N:29])[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]2)=[CH:17][CH:16]=1.[FH:30].[FH:31].F.C(N(CC)CC)C>C(Cl)Cl>[Cl:14][C:15]1[N:20]=[CH:19][C:18]([C:21]2([C:28]#[N:29])[CH2:26][CH2:25][C:24]([F:31])([F:30])[CH2:23][CH2:22]2)=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 175505N,N-Diethylethanamine trihydrofluorideHCID 44517918(Diethylamino)(difluoro)sulfanium tetrafluoroborateHCID 86716175HCID 86716175, compound

Product 1

HCID 86716176HCID 86716176, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of (diethylamino)difluorosulfonium tetrafluoroborate (16.5 g, 72.1 mmol) in DCM (150 mL) at room temperature under nitrogen atmosphere was added 1-(6-chloro-pyridin-3-yl)-4-oxo-cyclohexanecarbonitrile (4.2 g, 18 mmol) followed by triethylamine trihydrofluoride (8.68 g, 53.8 mmol). The reaction mixture was stirred for 6 hours at room temperature. The resulting mixture was then quenched by adding a saturated aqueous solution of sodium bicarbonate, stirred for 10 minutes, and the resulting mixture was extracted with DCM (3×25 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by column chromatography on silica gel (1:10 to 1:5 AcOEt/hexanes) to afford 1-(6-chloro-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrile (2.5 g, 54%). LC-MS (m/z) 257.0 (MH+). 1H NMR (400 MHz, CDCl3) δ ppm 8.56 (d, J=2.2 Hz, 1 H), 7.79 (dd, J=8.4, 2.6 Hz, 1 H), 7.42 (d, J=8.4 Hz, 1 H), 2.09-2.41 (m, 8 H).

Workup

  1. customThe resulting mixture was then quenched
  2. additionby adding a saturated aqueous solution of sodium bicarbonate
  3. stirringstirred for 10 minutes
  4. extractionthe resulting mixture was extracted with DCM (3×25 mL)
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by column chromatography on silica gel (1:10 to 1:5 AcOEt/hexanes)

Sources & evidence

ORD record
ord-13437e4b855943f48d8712fd3fa29ae2
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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