Methanol → HCID 59286714, compound

HRID 2196097Notes

Reaction equation

HRID 2196097 reaction equation
[CH3:1][O:2][C:3]1([O:9][CH3:10])[CH2:8][CH2:7][S:6][CH2:5][CH2:4]1.CO.COC1CCSCC=1.OC1C(O)=[C:29]([O:32][CH3:33])[CH:28]=[CH:27][C:23]=1[C:24]([OH:26])=[O:25]>CC1C=CC(S(O)(=O)=O)=CC=1.C(OCC)(=O)C>[CH3:33][O:32][C:29]1[C:1]2[O:2][C:3]3([O:9][C:10]=2[C:23]([C:24]([OH:26])=[O:25])=[CH:27][CH:28]=1)[CH2:8][CH2:7][S:6][CH2:5][CH2:4]3

Participants

7

Reactant 4

HCID 887MethanolHCID 775342,3-Dihydroxy-4-methoxybenzoic acidHCID 1233597761477-16-52×HCID 18934922HCID 18934922, compound

Product 1

HCID 59286714HCID 59286714, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
145 °C

Procedure

P-Toluenesulfonic acid (97 mg, 0.51 mmol) was added to 4,4-dimethoxytetrahydro-(4H)-thiopyran (20.7 g, 128 mmol) and the mixture was heated to 145° C. and kept at that temperature until approximately one equivalent of methanol (5.17 mL, 128 mmol) was distilled off. The mixture was then cooled to 130° C. and distillation under reduced pressure afforded 10.1 g of a 5:3 mixture of 5,6-dihydro-4-methoxy-(2H)-thiopyran [1H NMR (DMSO) δ 4.87 (m, 1H), 3.44 (s, 3H), 3.15 (dt, 2H), 2.72 (t, 2H), 2.22 (m, 2H)] and 4,4-dimethoxytetrahydro-(4H)-thiopyran. Without further purification the mixture was added to 2,3-dihydroxy-4-methoxybenzoic acid (2.00 g, 10.9 mmol) and the suspension was exposed to microwave heating (180° C., one hour) in a sealed reaction vessel. Ethyl acetate (100 mL) was added and the organic phase was first washed with 0.5 M HCl (40 mL) and then extracted with saturated aqueous NaHCO3 (2×30 mL). The aqueous phase was washed with Et2O (2×40 mL), acidified to pH=1 with concentrated HCl and extracted with dichloromethane (2×30 mL). The organic phase was dried over MgSO4. Evaporation under reduced pressure afforded 7-methoxy-2′,3′,5′,6′-tetrahydro-spiro[1,3-benzodioxole-2,4′-(4H)-thiopyran]-4-carboxylic acid (1.86 g, 61%). 13C NMR (DMSO) δ 164.9, 148.2, 146.6, 134.5, 123.8, 118.0, 107.2, 106.9, 56.1, 35.9, 25.4.

Workup

  1. distillationwas distilled off
  2. temperatureThe mixture was then cooled to 130° C.
  3. distillationdistillation under reduced pressure
  4. customafforded
  5. customWithout further purification the mixture
  6. temperatureheating (180° C., one hour)
  7. customin a sealed reaction vessel
  8. washthe organic phase was first washed with 0.5 M HCl (40 mL)
  9. extractionextracted with saturated aqueous NaHCO3 (2×30 mL)
  10. washThe aqueous phase was washed with Et2O (2×40 mL)
  11. extractionextracted with dichloromethane (2×30 mL)
  12. dry with materialThe organic phase was dried over MgSO4
  13. customEvaporation under reduced pressure

Sources & evidence

ORD record
ord-348ee00e2eef44f3a8139c2c30ce4d91
Source dataset
uspto-grants-2012_12
Patent number
US08338431B2

Reaction notes

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