Acetone → HCID 15840426, compound

HRID 2289303Notes

Reaction equation

HRID 2289303 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]([N:17]3[CH2:22][CH2:21][CH:20]([N:23]4[C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=5[CH2:26][O:25][C:24]4=[O:33])[CH2:19][CH2:18]3)=[O:16])=[C:10]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])[CH:9]=2)[CH2:3][CH2:2]1.CC([O-])=O.[Na+].[CH3:45][C:46]([CH3:48])=O.[BH3-]C#N.[Na+].Cl>CCO.CCOC(C)=O>[CH3:45][CH:46]([N:1]1[CH2:2][CH2:3][CH:4]([O:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]([N:17]3[CH2:22][CH2:21][CH:20]([N:23]4[C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=5[CH2:26][O:25][C:24]4=[O:33])[CH2:19][CH2:18]3)=[O:16])=[C:10]([O:34][CH2:35][C:36]([F:39])([F:37])[F:38])[CH:9]=2)[CH2:5][CH2:6]1)[CH3:48]

Participants

8

Reactant 5

HCID 180Acetone2×HCID 313Hydrochloric AcidHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydride2×HCID 15840420HCID 15840420, compound

Product 1

HCID 15840426HCID 15840426, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of the hydrochloride salt of 1-(1-(4-(4-piperidinyloxy)-2-(2,2,2-trifluoroethoxy)phenylacetyl)piperidin-4-yl)-4H-3,1-benzoxazin-2(1H)-one (0.20 g, 0.30 mmol) from Example 2 in EtOH (3 mL) was added NaOAc (0.05 g, 0.6 mmol), acetone (0.027 mL, 0.37 mmol), powdered 3 angstrom molecular seives (approx. 100 mg). The mixture was stirred at ambient temperature for 1 h and NaBH3CN (0.021 mg, 0.34 mmol) was added. The mixture was stirred for 14 h at ambient temperature. More acetone (0.027 mL, 0.37 mmol), molecular seives (approx. 100 mg), and NaBH3CN (0.021 mg, 0.34 mmol) were added and the mixture was stirred at ambient temperature for 48 h. The mixture was diluted with EtOAc, filtered, and the solvents were removed under reduced pressure. The residue was partitioned between CH2Cl2 (50 mL) and saturated aqueous NaHCO3 (2×25 mL). The organic phase was dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was dissolved in EtOH (5 mL) and 1.5 equivalents of 6 N aqueous HCl was added. The solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (1 mL) and added to a rapidly stirred ether (20 mL). The precipitate was collected by filtration to give the hydrochloride salt of the title compound as an amorphous solid.

Workup

  1. stirringThe mixture was stirred for 14 h at ambient temperature
  2. stirringthe mixture was stirred at ambient temperature for 48 h
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customThe residue was partitioned between CH2Cl2 (50 mL) and saturated aqueous NaHCO3 (2×25 mL)
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. dissolutionThe residue was dissolved in EtOH (5 mL)
  10. customThe solvent was removed under reduced pressure
  11. dissolutionThe residue was dissolved in CH2Cl2 (1 mL)
  12. additionadded to a rapidly stirred ether (20 mL)
  13. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-74a3edd77e8648508f4ceda459775dff
Source dataset
uspto-grants-2000_07
Patent number
US06090805

Reaction notes

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