Methanesulfonyl chloride → HCID 70229960, compound

HRID 1976202Notes

Reaction equation

HRID 1976202 reaction equation
CS([Cl:5])(=O)=O.[CH3:6][O:7][C:8](=[O:45])[CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][C@@H:15]1[C@@H:19](/[CH:20]=[CH:21]/[C@@H:22]([O:30]C2CCCCO2)[C:23]([CH3:29])([CH3:28])[CH2:24][CH2:25][CH2:26][CH3:27])[C@H:18]([O:37]C2CCCCO2)[CH2:17][C@@H:16]1O.C(O)(=O)C.O.O1CCCC1>N1C=CC=CC=1.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH3:6][O:7][C:8](=[O:45])[CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][C@@H:15]1[C@@H:19](/[CH:20]=[CH:21]/[C@@H:22]([OH:30])[C:23]([CH3:29])([CH3:28])[CH2:24][CH2:25][CH2:26][CH3:27])[C@H:18]([OH:37])[CH2:17][C@H:16]1[Cl:5]

Participants

7

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 21877175AcOH THF waterHCID 70226769HCID 70226769, compound

Product 1

HCID 70229960HCID 70229960, compoundYield 44.4%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 1049PyridineSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
20 °C

Procedure

319 mg of methane sulfonic acid chloride is added at 0° C. to a solution of 1.00 g of (4Z,13E)-(9S,11R,15R)-9-hydroxy-16,16-dimethyl-11,15-bis-(tetrahydropyran-2-yloxy)-4,13-prostadienoic acid methyl ester in 10 ml of pyridine. It is stirred for 4 hours at 20° C. and the solution is added to a suspension of 9.99 g of tetrabutylammonium chloride in 10 ml of toluene. After 15-hours stirring at 0° C., it is stirred for another 7 hours at 40° C. Then it is added to 100 ml of ice water and extracted three times with 50 ml each of ether. After the organic phase is washed twice with 20 ml of brine, dried over MgSO4 and is concentrated by evaporation in a vacuum a-residue is obtained which is chromatographed on silica gel with hexane/0-40% ether. 839 mg of oily (4Z,13E)-(9R,11R,15R)-9-chioro-16,16-dimethyl-11,15-bis(tetrahydropyran-2-yloxy)-4,13-prostaqienoic acid methyl ester is obtained. For cleavage of the protecting groups, the resulting ester is stirred with 31 ml of a mixture of acetic acid/water/ tetrahydrofuran (65/35/10) for 24 hours at 20° C. After addition of toluene and concentration of the solution by evaporation in a vacuum the residue is chromatographed on silica gel. With toluene/0-10% isopropanol as eluant, 326 mg of the title compound is obtained as colorless oil.

Workup

  1. stirringAfter 15-hours stirring at 0° C.
  2. stirringit is stirred for another 7 hours at 40° C
  3. extractionextracted three times with 50 ml each of ether
  4. washAfter the organic phase is washed twice with 20 ml of brine
  5. dry with materialdried over MgSO4
  6. concentrationis concentrated by evaporation in a vacuum a-residue
  7. customis obtained which
  8. customis chromatographed on silica gel with hexane/0-40% ether
  9. custom839 mg of oily (4Z,13E)-(9R,11R,15R)-9-chioro-16,16-dimethyl-11,15-bis(tetrahydropyran-2-yloxy)-4,13-prostaqienoic acid methyl ester is obtained
  10. customby evaporation in a vacuum the residue
  11. customis chromatographed on silica gel

Sources & evidence

ORD record
ord-a2b8104063a244778c949a2540997865
Source dataset
uspto-grants-2001_05
Patent number
US06225347B1

Reaction notes

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