Acetic Anhydride → N-[2-(8-Hydroxy-7-isopropyl-2-methyl-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)ethyl]acetamide

HRID 883264Notes

Reaction equation

HRID 883264 reaction equation
[OH:1][C:2]1([CH2:18][C:19]#[N:20])[C:13]2[C:12]3[O:11][C:10]([CH3:14])=[N:9][C:8]=3[CH:7]=[CH:6][C:5]=2[CH2:4][CH:3]1[CH:15]([CH3:17])[CH3:16].N.[CH2:22]([OH:24])[CH3:23].C(N(CC)CC)C.C(OC(=O)C)(=O)C.C(=O)([O-])O.[Na+]>C(O)C.[Co]>[OH:1][C:2]1([CH2:18][CH2:19][NH:20][C:22](=[O:24])[CH3:23])[C:13]2[C:12]3[O:11][C:10]([CH3:14])=[N:9][C:8]=3[CH:7]=[CH:6][C:5]=2[CH2:4][CH:3]1[CH:15]([CH3:17])[CH3:16]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 22020343Ethanol, reaction products with ammonia, distn. residuesHCID 57781236(8-Hydroxy-7-isopropyl-2-methyl-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)acetonitrile

Product 1

HCID 57781223N-[2-(8-Hydroxy-7-isopropyl-2-methyl-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)ethyl]acetamideYield 19%

Reagents, catalysts & solvents 2

HCID 104730CobaltCatalystHCID 702EthanolSolvent

Procedure

To a solution of (8-hydroxy-7-isopropyl-2-methyl-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)acetonitrile (584 mg, 2.16 mmol) in ethanol (11 mL) were added Raney cobalt (5.84 g) and 2M ammonia/ethanol solution (11 mL), and the mixture was stirred at room temperature for 24 hr under a hydrogen atmosphere. The catalyst was filtered off using celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (11 mL), triethylamine (82.9 μL, 0.594 mmol) and acetic anhydride (51.0 μL, 0.540 mmol) were added under ice-cooling, and the mixture was stirred for 5 min. To the reaction solution was added saturated aqueous sodium hydrogencarbonate solution, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) to give the title compound (132 mg, yield 19%).

Workup

  1. filtrationThe catalyst was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in tetrahydrofuran (11 mL)
  4. temperaturecooling
  5. stirringthe mixture was stirred for 5 min
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90)

Sources & evidence

ORD record
ord-6190947c7262428d83066ffc6b256d62
Source dataset
uspto-grants-2012_08
Patent number
US08236837B2

Reaction notes

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