Diethyl Ether → HCID 69128467, compound

HRID 2064217Notes

Reaction equation

HRID 2064217 reaction equation
[Br:1][C:2]1[C:3]([C:26]([F:29])([F:28])[F:27])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]4([C:23]#N)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[CH2:13][CH2:12]3)[C:6]=2[CH:25]=1.C[Mg]Br.C(OCC)C.[NH4+].[Cl-:39]>O1CCCC1.O>[ClH:39].[Br:1][C:2]1[C:3]([C:26]([F:27])([F:28])[F:29])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:12][CH2:13][N:14]([C:17]4([CH3:23])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)[CH2:15][CH2:16]3)[C:6]=2[CH:25]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 59850202HCID 59850202, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 69128467HCID 69128467, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A stirred suspension of 4-{4-[6-bromo-2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-piperidinyl}tetrahydro-2H-pyran-4-carbonitrile (D70, 1100 mg, 0.21 mmol) in tetrahydrofuran (8 ml) at room temperature under argon was treated with 3M methylmagnesium bromide solution in diethyl ether (0.15 ml, 0.46 mmol) and the insoluble material rapidly dissolved. Further methylmagnesium bromide solution was added after a total of 50 minutes (0.15 ml) and a total of 70 minutes (0.20 ml). After another 15 minutes the reaction mixture was cooled to 0° C. and treated dropwise with 1M aq. NH4Cl solution (3 ml), then diluted with water (15 ml) and extracted with ethyl acetate. The extract was washed with brine, dried (Na2SO4) and concentrated under vacuum to afford the title compound as a white solid. This was converted to its HCl salt as a white solid (95 mg, 90%).

Workup

  1. dissolutionthe insoluble material rapidly dissolved
  2. customa total of 70 minutes (0.20 ml)
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-25331d61deaf45d19cc0d475a8109b1c
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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