Toluene → HCID 178438729, compound

HRID 1412229Notes

Reaction equation

HRID 1412229 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:29]2[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:10](=[O:28])[N:11]([C@H:21]2[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23][CH2:22]2)[C:12]2[N:13]([N:18]=[CH:19][N:20]=2)[C:14]=1[CH2:15][CH2:16][CH3:17].Br[CH:38]([CH3:46])[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40].C1(C)C=CC=CC=1.[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:35]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:9]2[C:10](=[O:28])[N:11]([C@H:21]3[CH2:26][CH2:25][C@H:24]([O:27][CH:38]([CH3:46])[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:23][CH2:22]3)[C:12]3[N:13]([N:18]=[CH:19][N:20]=3)[C:14]=2[CH2:15][CH2:16][CH3:17])=[C:2]([F:1])[CH:3]=1)#[N:36]

Participants

7

Reactant 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 545327tert-Butyl 2-bromopropanoateHCID 178438709HCID 178438709, compound

Product 1

HCID 178438729HCID 178438729, compoundYield 96.1%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolvent

Procedure

To a mixture of 3′-fluoro-4′-{[4-(trans-4-hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (233 g), tert-butyl 2-bromopropanoate (301 g), toluene (1.7 L) and 50% sodium hydroxide (1.7 L) was added tetrabutylammonium hydrogen sulfate (16.3 g), and the mixture was stirred with the internal temperature maintained below 30° C. for 16 hr. Water (1 L) was slowly added under ice-cooling, and phases were separated. The aqueous layer was extracted with tetrahydrofuran (1.0 L). The combined extracts were successively washed with 3M hydrochloric acid (1 L) and brine (1 L), dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as an amorphous pale-yellow solid (283 g, 96%).

Workup

  1. temperaturemaintained below 30° C. for 16 hr
  2. temperaturecooling
  3. customphases were separated
  4. extractionThe aqueous layer was extracted with tetrahydrofuran (1.0 L)
  5. washThe combined extracts were successively washed with 3M hydrochloric acid (1 L) and brine (1 L)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-30feb40357c2449a85fc66fca5fc8c74
Source dataset
uspto-grants-2014_12
Patent number
US08921379B2

Reaction notes

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