Acetamide → HCID 117738800, compound

HRID 1754854Notes

Reaction equation

HRID 1754854 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@:8]23[CH2:15][O:14][CH2:13][C@H:12]2[CH2:11][O:10][N:9]3[C@@H:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:17][CH3:18])[CH:7]=1.[C:26]([NH2:29])(=[O:28])[CH3:27].[I-].[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CN(C)CCN>[Cu]I.CN(C=O)C>[F:25][C:5]1[CH:4]=[CH:3][C:2]([NH:29][C:26](=[O:28])[CH3:27])=[CH:7][C:6]=1[C@:8]12[CH2:15][O:14][CH2:13][C@H:12]1[CH2:11][O:10][N:9]2[C@@H:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:17][CH3:18]

Participants

8

Reactant 5

HCID 178AcetamideHCID 4875Potassium IodideHCID 62657Potassium Phosphate, TribasicHCID 66053N,N-DimethylethylenediamineHCID 117739055HCID 117739055, compound

Product 1

HCID 117738800HCID 117738800, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture of (3aS,6aS)-6a-(5-bromo-2-fluorophenyl)-1-((R)-1-phenylpropyl)hexahydrofuro[3,4-c]isoxazole (1.0 equiv., volumes are in mL/g of this compound), acetamide (4 equiv.), copper (I) iodide (0.2 equiv.), potassium iodide (0.7 equiv.), K3PO4 (2.0 equiv.), N,N-dimethylethylenediamine (0.8 equiv.) and DMF (4 mL/g) is heated at 110° C. for about 4 hours. After cooling to 30° C., the mixture is partitioned between isopropyl acetate (3.7 mL/g) and 10 weight % NH4Cl (5.7 mL/g) in water. The layers are separated and the aqueous layer is extracted with isopropyl acetate (2 mL/g). The combined organic layers are washed twice with 10 weight % NH4Cl (1 mL/g) in water. The organic layer is mixed with xylenes (4.3 mL/g), and the mixture is distilled under vacuum to remove most of the isopropyl acetate and residual DMF. The mixture is cooled to 0° C., the solids are collected by filtration, rinsed twice with xylenes (0.7 mL/g) and dried to give the title compound. LC-MS (m/z): 385 (M+H).

Workup

  1. temperatureAfter cooling to 30° C.
  2. customthe mixture is partitioned between isopropyl acetate (3.7 mL/g) and 10 weight % NH4Cl (5.7 mL/g) in water
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted with isopropyl acetate (2 mL/g)
  5. washThe combined organic layers are washed twice with 10 weight % NH4Cl (1 mL/g) in water
  6. additionThe organic layer is mixed with xylenes (4.3 mL/g)
  7. distillationthe mixture is distilled under vacuum
  8. customto remove most of the isopropyl acetate and residual DMF
  9. temperatureThe mixture is cooled to 0° C.
  10. filtrationthe solids are collected by filtration
  11. washrinsed twice with xylenes (0.7 mL/g)
  12. customdried

Sources & evidence

ORD record
ord-eee29034f845426cb847520c56ac4608
Source dataset
uspto-grants-2015_10
Patent number
US09169271B2

Reaction notes

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