2-Chlorobenzaldehyde → rac-2-(2-Chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetonitrile

HRID 598048

Reaction equation

HRID 598048 reaction equation
Cl.[S:2]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[CH:4]=[CH:3]1.[C-:11]#[N:12].[Na+].[Cl:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]=O.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>O.CO>[Cl:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]([N:7]1[CH2:8][CH2:9][C:10]2[S:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)[C:11]#[N:12]

Participants

7

Reactant 4

HCID 69962-ChlorobenzaldehydeHCID 8929Sodium CyanideHCID 656671Sodium PyrosulfiteHCID 101763424,5,6,7-Tetrahydrothieno(3,2-c)pyridinium chloride

Product 1

HCID 11369741rac-2-(2-Chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
45 °C

Procedure

To a mixture of methanol (2.50 l) and water (250 ml) was charged 4,5,6,7 -tetrahydro-thieno[3,2-c]pyridine hydrochloride (500 g; 2.85 mol) with stirring. After stirring for 10 minutes, sodium cyanide (153.0 g; 3.12 mol) was added and stirred further for 40 minutes. 2-Chlorobenzaldehyde (392.1 g; 2.79 mol) was added slowly to this reaction mixture between 23-28° C. over a period of 1.5 hours. After the addition was over, the flask was heated in an oil bath between 40-50° C. and maintained at this temperature for 4.5 hours. After cooling the reaction mixture to 25-30° C., 5% sodium metabisulfite solution (250 ml) was added and stirred for 1 hour at this temperature range. To the resulting slurry, water (7.5 l) was added and stirred for 1 hour at 25-30° C. The off-white solid thus formed was filtered, washed with a 1:1 mixture of methanol: water (2.5 l) and the wet cake was dried at 75° C. under vacuum (pressure: −0.8 kg/cm2) for 10 hours to obtain the product as an off-white solid. Yield: 719.0 g (87.4%). mp: 124-126.5° C. The product was identified by IR spectrum, 1H and 13C NMR investigation.

Workup

  1. stirringAfter stirring for 10 minutes
  2. stirringstirred further for 40 minutes
  3. additionAfter the addition
  4. temperaturemaintained at this temperature for 4.5 hours
  5. temperatureAfter cooling the reaction mixture to 25-30° C.
  6. stirringstirred for 1 hour at this temperature range
  7. stirringstirred for 1 hour at 25-30° C
  8. customThe off-white solid thus formed
  9. filtrationwas filtered
  10. washwashed with a 1:1 mixture of methanol
  11. dry with materialwater (2.5 l) and the wet cake was dried at 75° C. under vacuum (pressure: −0.8 kg/cm2) for 10 hours

Sources & evidence

ORD record
ord-1526f16a7c7f4f9a980dff9fd2c714e0
Source dataset
uspto-grants-2011_03
Patent number
US07897613B2

Linked notes

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