Methanol → 2'-chloro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] hydrochloride

HRID 1517557Notes

Reaction equation

HRID 1517557 reaction equation
[S:1]1[C:5]2[C:6]3([CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)[O:7][CH2:8][CH2:9][C:4]=2[CH:3]=[CH:2]1.S(Cl)([Cl:18])(=O)=O.CO>C(O)(=O)C.C(OC)(C)(C)C>[ClH:18].[Cl:18][C:2]1[S:1][C:5]2[C:6]3([CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)[O:7][CH2:8][CH2:9][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 24648Sulfuryl chloride2×HCID 529515494',5'-Dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]

Product 1

HCID 671670092'-chloro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] hydrochlorideYield 60%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent3×HCID 15413tert-Butyl methyl etherSolvent3×

Conditions

Temperature
15 °C

Procedure

A solution of 4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran] (50 g, 238.88 mmol) in a mixture of acetic acid (400 mL) and methyl t-butyl ether (40 mL) is cooled to 15° C. Then, a solution of sulfuryl chloride (21.20 mL, 262.77 mmol) in acetic acid (100 mL) is added dropwise in 40 min at that temperature (internal temperature=15° C.-22° C.) and the mixture is stirred at room temperature for 20 hr. Then, a solution of sulfuryl chloride (11.56 mL, 143.33 mmol) in acetic acid (50 mL) is added dropwise at room temperature. The reaction mixture is stirred at room temperature for 30 min. and then it is added dropwise (30 min) over methyl t-butyl ether (1 L) cooling with ice/water bath with stirring. A white suspension is formed and the solid is filtered. To obtain a second crop of material, the filtrate is concentrated (refilling with methyl t-butyl ether via rotavap). Resulting solid is suspended in methyl t-butyl ether (300 mL), suspension is stirred at reflux (bath: 100° C.) and methanol (30 mL) is added till a cloudy suspension is formed. Then, the suspension is cooled to room temperature overnight. The suspension is further cooled in a ice/water bath and filtered. Solid is washed with methyl t-butyl ether (50 mL) and combined with first crop to give the title compound in a 60% yield. MS (m/z): 244 (M+1).

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 30 min.
  2. temperaturecooling with ice/water bath
  3. stirringwith stirring
  4. customA white suspension is formed
  5. filtrationthe solid is filtered
  6. customTo obtain a second crop of material
  7. concentrationthe filtrate is concentrated (refilling with methyl t-butyl ether via rotavap)
  8. customResulting solid
  9. stirringsuspension is stirred
  10. additionis added till a cloudy suspension
  11. customis formed
  12. temperatureThen, the suspension is cooled to room temperature overnight
  13. temperatureThe suspension is further cooled in a ice/water bath
  14. filtrationfiltered
  15. washSolid is washed with methyl t-butyl ether (50 mL)

Sources & evidence

ORD record
ord-90291966decb458b8f07096c6e1c533f
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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