Dimethyl Sulfoxide → HCID 25209257, compound

HRID 1874115Notes

Reaction equation

HRID 1874115 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]([F:50])([CH2:46][CH2:47][CH2:48][CH3:49])[CH:13]([OH:45])[CH2:14][CH2:15][C@H:16]1[C@H:20]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH2:19][C@H:18]([OH:28])[C@@H:17]1[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36].C(N(CC)CC)C.O.[NH4+]>ClCCl>[F:50][C:12]([F:11])([CH2:46][CH2:47][CH2:48][CH3:49])[C:13](=[O:45])[CH2:14][CH2:15][C@H:16]1[C@H:20]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH2:19][C:18](=[O:28])[C@@H:17]1[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH2:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)=[O:36]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 22024077Azanium;hydrateHCID 24875734HCID 24875734, compound

Product 1

HCID 25209257HCID 25209257, compoundYield 96.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of oxalyl chloride (57.0 ml, 653 mmol) in dichloromethane (635 ml) was cooled in a dry ice-methanol bath. Dimethylsulfoxide (92.7 ml, 1306 mmol) was added drop wise and the solution was stirred for 30 minutes. A solution of benzyl 7-[(1R,2R,3R,5S)-2-(4,4-difluoro-3-hydroxyoctyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (18) (74.31 g, 130.7 mmol) in dichloromethane (191 ml) was added drop wise, and the mixture was stirred for approximately 1.5 hours. Triethylamine (273 ml, 1959 mmol) was added drop wise to the mixture and the reaction mixture was warmed to 0° C., saturated ammonium water (605 ml) was added to the solution and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with dichloromethane (302 ml). The organic layers were combined and sequentially washed with 0.35N-hydrochloric acid (302 ml), water (605 ml), saturated sodium bicarbonate water (605 ml) and saturated aqueous sodium chloride (605 ml). After drying with anhydrous magnesium sulfate (52 g), the solution was concentrated under reduced pressure. The residue was dissolved in a suitable amount of ethyl acetate/hexane solvent mix (1:10), and insoluble matter was filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2260 g; ethyl acetate:hexane=1:4) to give benzyl 7-[(1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-5-oxo-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (19) (71.44 g; 126.5 mmol; yield: 96.8%) as a pale yellow oil.

Workup

  1. stirringthe mixture was stirred for approximately 1.5 hours
  2. stirringthe mixture was stirred
  3. customseparated into two layers
  4. extractionThe aqueous layer was extracted twice with dichloromethane (302 ml)
  5. washsequentially washed with 0.35N-hydrochloric acid (302 ml), water (605 ml), saturated sodium bicarbonate water (605 ml) and saturated aqueous sodium chloride (605 ml)
  6. dry with materialAfter drying with anhydrous magnesium sulfate (52 g)
  7. concentrationthe solution was concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in a suitable amount of ethyl acetate/hexane solvent
  9. additionmix (1:10), and insoluble matter
  10. filtrationwas filtered
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2260 g; ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-1bdb9524bd644031ac86edf7aa97e8bc
Source dataset
uspto-grants-2012_11
Patent number
US08304562B2

Reaction notes

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