Ammonium Chloride → 5-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazole-2-carbonitrile

HRID 561196Notes

Reaction equation

HRID 561196 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.C(N(CC)C(C)C)(C)C.Br[C:26]1[S:30][C:29]([C:31]#[N:32])=[N:28][N:27]=1.[NH4+].[Cl-]>O1CCOCC1>[Br:1][C:2]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:3]=1[O:4][CH:5]1[CH2:6][CH2:7][N:8]([C:26]2[S:30][C:29]([C:31]#[N:32])=[N:28][N:27]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 533885265-Bromo-1,3,4-thiadiazole-2-carbonitrileHCID 578327574-(2-Bromo-5-fluorophenoxy)piperidine

Product 1

HCID 533885275-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazole-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-(2-bromo-5-fluorophenoxy)piperidine (15.16 g, 52.5 mmol) in 1,4-dioxane (80 mL) was added N,N-diisopropylethylamine (Hünig's base or DIPEA) (20 mL, 115 mmol) followed by 5-bromo-1,3,4-thiadiazole-2-carbonitrile (10.02 g, 52.7 mmol). The mixture was stirred 1 h at room temperature. The reaction mixture was then poured into saturated aqueous NH4Cl, extracted with EtOAc, washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel (eluting with 10-40% EtOAc/hexanes) to afford the desired product as a colorless oil.

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by column chromatography on silica gel (eluting with 10-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e03d8667e336406089bae1ecb26816ff
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

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