Ethanol → HCID 59516141, compound

HRID 1799429Notes

Reaction equation

HRID 1799429 reaction equation
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:23]3[CH:28]=[CH:27][C:26](Cl)=[CH:25][C:24]=3[CH3:30])[C:18]=1[C:19]([CH3:22])([CH3:21])[CH3:20])=[O:13])[CH2:8]2.C(N(C(C)C)C(C)C)C.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.O1C[CH2:62][O:61][CH2:60][CH2:59]1.C([OH:66])C>CN(C)C1C=CN=CC=1.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:23]3[CH:28]=[CH:27][C:26]([C:62]([O:61][CH2:60][CH3:59])=[O:66])=[CH:25][C:24]=3[CH3:30])[C:18]=1[C:19]([CH3:22])([CH3:21])[CH3:20])=[O:13])[CH2:8]2

Participants

9

Reactant 5

HCID 702EthanolHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 44558591Tri-t-butylphosphine fluoroborateHCID 59516130N-(2-adamantyl)-1-(4-chloro-2-methyl-phenyl)-5-tert-butyl-pyrazole-4-carboxamide2×

Product 1

HCID 59516141HCID 59516141, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Conditions

Temperature
150 °C

Procedure

N-(2-adamantyl)-1-(4-chloro-2-methyl-phenyl)-5-tert-butyl-pyrazole-4-carboxamide (Intermediate #114) (647 mg, 1.52 mmol), Molybdenum hexacarbonyl (0.102 mL, 0.76 mmol), 4-Dimethylaminopyridine (371 mg, 3.04 mmol), N-Ethyldiisopropylamine (0.529 mL, 3.04 mmol), trans-Di-mu-acetatobis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) (71.4 mg, 0.08 mmol) and Tri-tert-butylphosphine tetrafluoroborate (88 mg, 0.30 mmol) were suspended in ethanol (6 mL) and dioxane (6.00 mL) and sealed into a microwave tube. The reaction was heated to 150° C. for 1 hour in the microwave reactor and cooled to RT. The reaction mixture was evaporated to dryness and redissolved in EtOAc (100 mL), and washed with water (10 mL), filtered, then washed with 2M HCl (10 mL), and saturated brine (10 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 2.5% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford ethyl 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]-3-methyl-benzoate (352 mg, 50.0%) as a colourless oil.

Workup

  1. temperaturecooled to RT
  2. customThe reaction mixture was evaporated to dryness
  3. dissolutionredissolved in EtOAc (100 mL)
  4. washwashed with water (10 mL)
  5. filtrationfiltered
  6. washwashed with 2M HCl (10 mL), and saturated brine (10 mL)
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto afford crude product
  11. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 2.5% EtOAc in isohexane
  12. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-d889c6674c8e44618fdef2111b17b10c
Source dataset
uspto-grants-2013_01
Patent number
US08344016B2

Reaction notes

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