Acetone Cyanohydrin → 4-[4-(6-fluoro-5-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)-1-piperidinyl]tetrahydro-2H-pyran-4-carbonitrile

HRID 1798919Notes

Reaction equation

HRID 1798919 reaction equation
[F:1][C:2]1[C:17]([CH3:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[C:7](=[O:9])[O:8][C:4]=2[CH:3]=1.S([O-])([O-])(=O)=O.[Mg+2].[CH3:25][C:26]([CH3:30])(O)[C:27]#[N:28].[O:31]1[CH2:36]CC(=O)C[CH2:32]1>CN(C)C(=O)C.ClCCl.O>[F:1][C:2]1[C:17]([CH3:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:11][CH2:12][N:13]([C:26]4([C:27]#[N:28])[CH2:30][CH2:36][O:31][CH2:32][CH2:25]4)[CH2:14][CH2:15]3)[C:7](=[O:9])[O:8][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 6406Acetone CyanohydrinHCID 24083Sulfuric acid magnesium salt (1:1)HCID 121599Tetrahydro-4H-pyran-4-oneHCID 67220395HCID 67220395, compound

Product 1

HCID 582873204-[4-(6-fluoro-5-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)-1-piperidinyl]tetrahydro-2H-pyran-4-carbonitrileYield 207.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

6-Fluoro-5-methyl-3-(4-piperidinyl)-1,3-benzoxazol-2(3H)-one (D3, 318 mg, 0.915 mmol) was dissolved in N,N-dimethylacetamide (10 mL) at rt under argon. Magnesium sulfate (562 mg, 4.67 mmol), acetone cyanohydrin (0.17 mL, 1.86 mmol) and tetrahydro-4H-pyran-4-one (0.17 mL, 1.84 mmol) were added and the reaction was heated at 70° C. for 24 h under a gentle stream of argon. The mixture was then cooled to rt, diluted with 1:1 dichloromethane:water (30 mL) and sonicated for 20 min. The phases were allowed to separate and the organic phase was dried by filtering through a hydrostatic cartridge. A further 10 mL of dichloromethane was added to the aqueous phase and the mixture stirred vigorously for 10 min. The 2 phases were again separated and the organic phase was dried by filtering through a hydrostatic cartridge. The combined organic layers were concentrated by rotary evaporation to give 4-[4-(6-fluoro-5-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)-1-piperidinyl]tetrahydro-2H-pyran-4-carbonitrile (D4, 681 mg, 45% purity, 93% yield) as an orange solid.

Workup

  1. temperatureThe mixture was then cooled to rt
  2. customto separate
  3. customthe organic phase was dried
  4. filtrationby filtering through a hydrostatic cartridge
  5. additionA further 10 mL of dichloromethane was added to the aqueous phase
  6. customThe 2 phases were again separated
  7. customthe organic phase was dried
  8. filtrationby filtering through a hydrostatic cartridge
  9. concentrationThe combined organic layers were concentrated by rotary evaporation

Sources & evidence

ORD record
ord-b1d2e46f47e241aa80b217365ea70c5c
Source dataset
uspto-grants-2013_01
Patent number
US08344000B2

Reaction notes

Loading…