HCID 178418573, compound → HCID 178438718, compound

HRID 1688487Notes

Reaction equation

HRID 1688487 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2[C:17](=[O:44])[N:18]([C@H:28]3[CH2:33][CH2:32][C@H:31]([O:34][CH:35]([CH3:43])C(OC(C)(C)C)=O)[CH2:30][CH2:29]3)[C:19]3[N:20]([N:25]=[CH:26][N:27]=3)[C:21]=2[CH2:22][CH2:23][CH3:24])=[C:11]([F:45])[CH:10]=1)#[N:2].C[Mg]Br>O1CCCC1>[F:45][C:11]1[CH:10]=[C:9]([C:4]2[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:14]=[CH:13][C:12]=1[CH2:15][C:16]1[C:17](=[O:44])[N:18]([C@H:28]2[CH2:29][CH2:30][C@H:31]([O:34][CH:35]([CH3:43])[C:31]([OH:34])([CH3:32])[CH3:30])[CH2:32][CH2:33]2)[C:19]2[N:20]([N:25]=[CH:26][N:27]=2)[C:21]=1[CH2:22][CH2:23][CH3:24]

Participants

4

Reactant 2

HCID 178418573HCID 178418573, compoundHCID 178438729HCID 178438729, compound

Product 1

HCID 178438718HCID 178438718, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 2-[(trans-4-{6-[(2′-cyano-3-fluorobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclohexyl)oxy]propanoate (548 g) was dissolved in tetrahydrofuran (2.7 L), and methylmagnesium bromide (1.0 M tetrahydrofuran solution, 3.5 L) was added with the internal temperature maintained below 10° C. The reaction mixture was stirred at the same temperature for 1 hr, and partitioned among saturated aqueous ammonium chloride solution (600 mL), water (600 mL) and ethyl acetate (500 mL). The aqueous layer was extracted with ethyl acetate (1 L). The combined extracts were washed with saturated brine (1 L), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound as a racemate (428 g, 84%).

Workup

  1. temperaturemaintained below 10° C
  2. custompartitioned among saturated aqueous ammonium chloride solution (600 mL), water (600 mL) and ethyl acetate (500 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (1 L)
  4. washThe combined extracts were washed with saturated brine (1 L)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a45ef6ae22e640079d72684496f27db4
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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