Acetic Acid → HCID 15840423, compound

HRID 2289301Notes

Reaction equation

HRID 2289301 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([N:18]3[CH2:23][CH2:22][CH:21]([N:24]4[C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=5[CH2:27][O:26][C:25]4=[O:34])[CH2:20][CH2:19]3)=[O:17])=[C:11]([O:35][CH2:36][C:37]([F:40])([F:39])[F:38])[CH:10]=2)[CH2:4][CH2:3]1.C([O-])(=O)C.[Na+].C(O)(=O)C.[CH:50]1([CH:53]=O)[CH2:52][CH2:51]1.[BH3-]C#N.[Na+]>CO.Cl>[CH:50]1([CH2:53][N:2]2[CH2:3][CH2:4][CH:5]([O:8][C:9]3[CH:14]=[CH:13][C:12]([CH2:15][C:16]([N:18]4[CH2:23][CH2:22][CH:21]([N:24]5[C:29]6[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=6[CH2:27][O:26][C:25]5=[O:34])[CH2:20][CH2:19]4)=[O:17])=[C:11]([O:35][CH2:36][C:37]([F:40])([F:38])[F:39])[CH:10]=3)[CH2:6][CH2:7]2)[CH2:52][CH2:51]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 18700152HCID 18700152, compound

Product 1

HCID 15840423HCID 15840423, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent2×

Procedure

To a solution of 1-(1-(4-(4-piperidinyloxy)-2-(2,2,2-trifluoroethoxy)phenylacetyl)piperidin-4-yl)-4H-3,1-benzoxazin-2(1H)-one hydrochloride (0.30 g, 0.5 mmol) from Example 2 in MeOH (7.5 mL) was added sodium acetate (82 mg, 1.0 mmol), acetic acid (0.10 mL, 1.7 mmol), and cyclopropane carboxaldehyde (75 mg, 1.1 mmol). The mixture was stirred at ambient temperature for 30 min and NaBH3CN (61 mg, 1.0 mmol) was added. The solution was stirred for 18 h and the solvent was removed under reduced pressure. The residue was dissolved in EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (3×25 mL). The organic phase was dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 97:3:0.3 CH2Cl2 :MeOH:NH4OH as eluant. The free base was dissolved in MeOH containing 1.5 equivalents of 3 N aqueous HCl. The resulting solution was evaporated under reduced pressure and the residue was lyophilized from CH3CN:H2O to give the hydrochloride salt of the title compound as an amorphous solid.

Workup

  1. stirringThe solution was stirred for 18 h
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in EtOAc (50 mL)
  4. washwashed with saturated aqueous NaHCO3 (3×25 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by pressurized silica gel column chromatography
  9. customThe resulting solution was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6a1304beb7c4478a9080b34ecaece56c
Source dataset
uspto-grants-2000_07
Patent number
US06090805

Reaction notes

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