Toluene → HCID 178438729, compound

HRID 519514Notes

Reaction equation

HRID 519514 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-55ed8eece9884d5c9ea9523b3bc37420
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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