p-Toluenesulfonic acid monohydrate → HCID 54710292, compound

HRID 2293703Notes

Reaction equation

HRID 2293703 reaction equation
[C:1]1([NH:7][S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]([CH:19]3[CH2:21][CH2:20]3)O)[CH:12]=2)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:22][C:23]1[C:24]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][C:25]=2[O:26][C:27](=[O:29])[CH:28]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[C:1]1([NH:7][S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]([CH:19]3[CH2:21][CH2:20]3)[C:28]3[C:27](=[O:29])[O:26][C:25]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][C:24]=4[C:23]=3[OH:22])[CH:12]=2)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 10780761HCID 10780761, compoundHCID 547293054-Hydroxy-5,6,7,8,9,10-hexahydro-2H-cycloocta[b]pyran-2-one

Product 1

HCID 54710292HCID 54710292, compoundYield 10.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 437 mg of N-phenyl-3-(cyclopropylhydroxymethyl)-benzenesulfonamide of Preparation 88 in 100 mL of dichloromethane in the presence of molecular sieves 3A is added 282.5 mg of 4-hydroxy-5,6,7,8,9,10-hexahydro-cycloocta[b]pyran-2-one of formula BBB-followed by 52.0 mg of p-toluenesulfonic acid monohydrate. The reaction is heated at reflux for 1 h and 30 min and then concentrated in vacuo. The resulting oil is dissolved in ethyl acetate and treated with water and 1N aqueous sodium hydroxide. The layers are separated and the organic layer is washed with a second portion of 1N aqueous sodium hydroxide. The combined aqueous layers are treated with 5% aqueous hydrochloric acid and extracted with three portions of ethyl acetate. The combined organics are dried (sodium sulfate) (Na2SO4) and concentrated to afford a yellow oil which is chromatographed over 80 g of silica (eluted with 15% hexane/ethyl acetate) to afford 74 mg of material. This material is rechromatographed as above (elution with 50% hexane/ethyl acetate) to afford 67.3 mg of the title product as a white solid.

Workup

  1. temperatureThe reaction is heated
  2. temperatureat reflux for 1 h and 30 min
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting oil is dissolved in ethyl acetate
  5. additiontreated with water and 1N aqueous sodium hydroxide
  6. customThe layers are separated
  7. washthe organic layer is washed with a second portion of 1N aqueous sodium hydroxide
  8. additionThe combined aqueous layers are treated with 5% aqueous hydrochloric acid
  9. extractionextracted with three portions of ethyl acetate
  10. dry with materialThe combined organics are dried (sodium sulfate) (Na2SO4)
  11. concentrationconcentrated
  12. customto afford a yellow oil which
  13. customis chromatographed over 80 g of silica (eluted with 15% hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3de7e4efbbf74a1695a76ffb39386d73
Source dataset
uspto-grants-1997_11
Patent number
US05686486

Reaction notes

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