Sodium Chloride → HCID 24875829, compound

HRID 899555Notes

Reaction equation

HRID 899555 reaction equation
[F:1][C:2]([F:40])([CH2:36][CH2:37][CH2:38][CH3:39])[C:3](=[O:35])[CH2:4][CH2:5][C@H:6]1[C@H:10]([O:11]C2CCCCO2)[CH2:9][C:8](=[O:18])[C@@H:7]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].[Cl-].[Na+]>C(#N)C.O.P(=O)(O)(O)O>[F:1][C:2]([C@:3]1([OH:35])[O:11][C@@H:10]2[CH2:9][C:8](=[O:18])[C@H:7]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[C@H:6]2[CH2:5][CH2:4]1)([F:40])[CH2:36][CH2:37][CH2:38][CH3:39]

Participants

6

Reactant 2

HCID 5234Sodium ChlorideHCID 25209257HCID 25209257, compound

Product 1

HCID 24875829HCID 24875829, compoundYield 87.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1004Phosphoric AcidSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of benzyl 7-[(1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-5-oxo-3-(2-tetrahydropyranyloxy) cyclopentyl]heptanoate (1) (70.49 g, 124.8 mmol) in acetonitrile (705 ml), water (70.5 ml) and 85% aqueous phosphoric acid (70.5 ml) were added, and the mixture was stirred for three hours at about 20° C. 10% aqueous sodium chloride (705 ml) was added to the mixture and the mixture was extracted with ethyl acetate (276 ml) for 3 times. The organic layers were combined and washed with 10% aqueous sodium chloride (360 ml), saturated aqueous sodium bicarbonate (360 ml) and saturated aqueous sodium chloride (360 ml) successively, dried with anhydrous magnesium sulfate (51 g) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300 2100 g, ethyl acetate:hexane=1:4). Fractions containing impurities were purified again by silica gel column chromatography (Fuji Silysia BW-300 1000 g, ethyl acetate:hexane=1:4) to give benzyl 7-[(2R,4aR,5R,7aR)-2-(1,1-difluoropentyl)-2-hydroxy-6-oxooctahydrocyclopenta[b]pyran-5-yl]heptanate (2) (52.64 g, 109.5 mmol, yield: 87.8%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (276 ml) for 3 times
  2. washwashed with 10% aqueous sodium chloride (360 ml), saturated aqueous sodium bicarbonate (360 ml) and saturated aqueous sodium chloride (360 ml) successively
  3. dry with materialdried with anhydrous magnesium sulfate (51 g)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (Fuji Silysia BW-300 2100 g, ethyl acetate:hexane=1:4)
  6. additionFractions containing impurities
  7. customwere purified again by silica gel column chromatography (Fuji Silysia BW-300 1000 g, ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-fbe044b6504341b69118f690000e4754
Source dataset
uspto-grants-2008_04
Patent number
US07355064B2

Reaction notes

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