Hydrochloric Acid → HCID 117738290, compound

HRID 1754855Notes

Reaction equation

HRID 1754855 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[CH:4][C:3]=1[C@:12]12[CH2:19][O:18][CH2:17][C@H:16]1[CH2:15][O:14][N:13]2[C@@H](C1C=CC=CC=1)CC.C(O)CC.[ClH:33]>[Pd].[Cl-].[Zn+2].[Cl-].O>[ClH:33].[NH2:13][C@:12]1([C:3]2[CH:4]=[C:5]([NH:8][C:9](=[O:11])[CH3:10])[CH:6]=[CH:7][C:2]=2[F:1])[C@H:16]([CH2:15][OH:14])[CH2:17][O:18][CH2:19]1

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 10311-PropanolHCID 117738800HCID 117738800, compound

Product 1

HCID 117738290HCID 117738290, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 3007855ZincchlorideCatalystHCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of N-(4-fluoro-3-((3aS,6aS)-1-((R)-1-phenylpropyl)hexahydrofuro[3,4-c]isoxazol-6a-yl)phenyl)acetamide (1.0 equiv., volumes are in mL/g of this compound), zinc chloride (0.2 equiv), and a 20% weight loading of water wet, sulfided 5% Pd/C catalyst is slurried in a mixture 1-propanol (4 mL/g), water (3.8 mL/g), and HCl (0.9 equiv, 33 weight % in water). The mixture is heated at 50° C. under hydrogen pressure (about 300-400 kPa) for about 16 hours. The catalyst is removed by filtration at about 50° C. and the filter cake is rinsed with 1-propanol (2.9 mL/g). Most of the water is removed from combined filtrates by azeotropic distillation using additional 1-propanol (10.5 mL/g). Additional HCl (0.1 equiv., 33 weight % in water) is added to the mixture and the solids are collected by filtration, rinsed twice with 1-propanol (1 mL/g) and dried to give the title compound. LC-MS (m/z): 269 (M+H).

Workup

  1. customThe catalyst is removed by filtration at about 50° C.
  2. washthe filter cake is rinsed with 1-propanol (2.9 mL/g)
  3. customMost of the water is removed
  4. distillationby azeotropic distillation
  5. filtrationthe solids are collected by filtration
  6. washrinsed twice with 1-propanol (1 mL/g)
  7. customdried

Sources & evidence

ORD record
ord-647e762a8c094b3a8269a14930245988
Source dataset
uspto-grants-2015_10
Patent number
US09169271B2

Reaction notes

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