Triethylamine → HCID 89704998, compound

HRID 1481353Notes

Reaction equation

HRID 1481353 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[Si]([C:17]#[N:18])(C)(C)C.Cl.[F:20][C:21]1([F:27])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.CCN(CC)CC.C([O-])([O-])=O.[Na+].[Na+]>CCOCC.CO.[Zn+2].[I-].[I-]>[F:20][C:21]1([F:27])[CH2:26][CH2:25][N:24]([CH:7]([C:6]2[CH:9]=[CH:10][C:3]([C:2]([F:12])([F:11])[F:1])=[CH:4][CH:5]=2)[C:17]#[N:18])[CH2:23][CH2:22]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 679964-(Trifluoromethyl)benzaldehydeHCID 82115Trimethylsilyl cyanideHCID 27583514,4-Difluoropiperidine hydrochloride

Product 1

HCID 89704998HCID 89704998, compound

Reagents, catalysts & solvents 3

HCID 9883512zinc(II)iodideCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 4-(trifluoromethyl)benzaldehyde (5.63 mmol) in 1 mL Et2O were added TMSCN (6.19 mmol) followed by ZnI2 (0.28 mmol). At 0° C., a solution of 4,4-difluoropiperidine HCl (6.19 mmol) and Et3N (11.8 mmol) in 5 mL MeOH was dropwise added maintaining the temperature below 10° C. The reaction mixture was then heated to reflux for 3 h. After cooling to RT, an aqueous solution of 10% Na2CO3 was added and the mixture was extracted 3 times with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification with CC (KP-NH™ from Biotage) using Hept to Hept/EtOAc (70/30) gives the desired compound as white solid.

Workup

  1. temperaturemaintaining the temperature below 10° C
  2. temperatureThe reaction mixture was then heated
  3. temperatureto reflux for 3 h
  4. extractionthe mixture was extracted 3 times with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification with CC (KP-NH™ from Biotage)

Sources & evidence

ORD record
ord-562f7bb4ca414e46ab8011458563a8f8
Source dataset
uspto-grants-2016_08
Patent number
US09409917B2

Reaction notes

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