Acetone Cyanohydrin → 4-(3-methyl-piperidino)-tetrahydro-4H-thiopyran-4-carbonitrile

HRID 1251365Notes

Reaction equation

HRID 1251365 reaction equation
S([O-])([O-])(=O)=O.[Mg+2].[CH3:7][C:8]([N:10](C)C)=O.[CH3:13][CH:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1.[S:20]1[CH2:25][CH2:24]C(=O)[CH2:22][CH2:21]1.CC(C)(O)C#N.N(ON)=O>CC(C)=O>[CH3:13][CH:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:7]2([C:8]#[N:10])[CH2:24][CH2:25][S:20][CH2:21][CH2:22]2)[CH2:15]1

Participants

8

Reactant 6

HCID 6406Acetone CyanohydrinHCID 24083Sulfuric acid magnesium salt (1:1)HCID 31374DimethylacetamideHCID 66173Tetrahydrothiopyran-4-one2×HCID 790813-MethylpiperidineHCID 21703181Amino nitrite

Product 1

HCID 183239454-(3-methyl-piperidino)-tetrahydro-4H-thiopyran-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
45 °C

Procedure

Magnesium sulphate (9.6 g, 80 mmoles), DMA (2 g, 23 mmoles), (±)-3-methylpiperidine (4 g, 40 mmoles), tetrahydro-4H-thiopyran-4-one (2.3 g, 20 mmoles) and acetone cyanohydrin (1.7 g, 20 mmoles) are introduced in succession into a 250 ml two-necked flask. The reaction medium is agitated for 48 hours at 45° C. After cooling down to ambient temperature, the pasty mixture obtained is placed on ice (approximately 150) and agitated for 30 minutes. Extraction with ether is then carried out (3×80 ml), the combined organic phases are washed with water (100 ml), followed by drying over Na2SO4, filtering and concentration to dryness. A brown oil is thus obtained (4.5 g, 20 mmoles) constituted by a mixture of expected product with approximately 4% of amino nitrite originating from acetone and 7% of the remaining tetrahydro-4H-thiopyran-4-one. The product is then used without further purification.

Workup

  1. temperatureAfter cooling down to ambient temperature
  2. customthe pasty mixture obtained
  3. stirringagitated for 30 minutes
  4. extractionExtraction with ether
  5. washthe combined organic phases are washed with water (100 ml)
  6. dry with materialby drying over Na2SO4
  7. filtrationfiltering
  8. concentrationconcentration to dryness
  9. customA brown oil is thus obtained (4.5 g, 20 mmoles)

Sources & evidence

ORD record
ord-5bd7d50a09be47ba8580f26c5ee364d3
Source dataset
uspto-grants-2002_01
Patent number
US06342511B1

Reaction notes

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