Propargyl alcohol → 2-cyclopentyl-4-(3-hydroxyprop-1-ynyl)-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonate

HRID 383426Notes

Reaction equation

HRID 383426 reaction equation
[C:1](=[O:35])([O:33][CH3:34])[O:2][C:3]1[CH:8]=[C:7]([NH:9][C:10]([CH:12]2[O:17][C:16]3[CH:18]=[CH:19][C:20]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:21][C:15]=3[NH:14][CH2:13]2)=[O:11])[C:6](Br)=[CH:5][C:4]=1[CH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1.C(N(CC)CC)C.[CH2:43]([OH:46])[C:44]#[CH:45].C([O-])(O)=O.[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:1](=[O:35])([O:33][CH3:34])[O:2][C:3]1[CH:8]=[C:7]([NH:9][C:10]([CH:12]2[O:17][C:16]3[CH:18]=[CH:19][C:20]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:21][C:15]=3[NH:14][CH2:13]2)=[O:11])[C:6]([C:45]#[C:44][CH2:43][OH:46])=[CH:5][C:4]=1[CH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

8

Reactant 4

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 593949824-Bromo-2-cyclopentyl-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonate

Product 1

HCID 593949372-cyclopentyl-4-(3-hydroxyprop-1-ynyl)-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonateYield 53%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

4-Bromo-2-cyclopentyl-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonate (812 mg, 1.45 mmol), triethylamine (2.0 mL, 14.52 mmol), prop-2-yn-1-ol (326 mg, 338 μL, 5.81 mmol), PdCl2(PPh3)2 (204 mg, 0.29 mmol), and CuI (69 mg, 0.36 mmol) were combined in DMF (6 mL) and heated at 80° C. for 1 h. The mixture was added to 300 mL of saturated aqueous NaHCO3 and then extracted with dichloromethane (3×70 mL). The organic fractions were combined, dried over MgSO4, and concentrated in vacuo. Purification by silica gel chromatography (0-100% ethyl acetate/hexanes) yielded 2-cyclopentyl-4-(3-hydroxyprop-1-ynyl)-5-(6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamido)phenyl methyl carbonate (410 mg, 53% yield). LC/MS m/z 535.4 [M+H]+.

Workup

  1. extractionextracted with dichloromethane (3×70 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customPurification by silica gel chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-446a59e373c04589a5904fedaec6499d
Source dataset
uspto-grants-2013_02
Patent number
US08367660B2

Reaction notes

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