HCID 25209257, compound → HCID 24875829, compound

HRID 899556Notes

Reaction equation

HRID 899556 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]>O1CCCC1.C(O)(=O)C.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

5

Reactant 1

HCID 25209257HCID 25209257, compound

Product 1

HCID 24875829HCID 24875829, compoundYield 75.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °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) (39.84 g, 70.54 mmol) in tetrahydrofuran (40 ml), acetic acid (260 ml) and water (140 ml) were added. The mixture was stirred at about 40° C. for 4 hours. The reaction was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia BW-300 1600 g, ethyl acetate:hexane=1:3). Fractions containing impurities were purified again by silica gel column chromatography (Fuji Silysia FL-60D 1600 g, ethyl acetate:hexane=1:4). Fractions still containing impurities were collected and further purified repeatedly with silica gel column chromatography (Fuji Silysia FL-60D 1000 g, IPA:hexane=8:100), (Fuji Silysia FL-60D 1600 g, IPA:hexane=7.5:100→3:40), (Fuji Silysia FL-60D 1600 g, IPA:hexane=3:40). Fractions containing substantially no impurities were collected and evaporated to give benzyl 7-[(2R,4aR,5R,7aR)-2-(1,1-difluoropentyl)-2-hydroxy-6-oxooctahydrocyclopenta[b]pyran-5-yl]heptanate (2) (25.68 g, 53.44 mmol, yield: 75.8%).

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (Fuji Silysia BW-300 1600 g, ethyl acetate:hexane=1:3)
  3. additionFractions containing impurities
  4. customwere purified again by silica gel column chromatography (Fuji Silysia FL-60D 1600 g, ethyl acetate:hexane=1:4)
  5. customFractions still containing impurities were collected
  6. customfurther purified repeatedly with silica gel column chromatography (Fuji Silysia FL-60D 1000 g, IPA:hexane=8:100), (Fuji Silysia FL-60D 1600 g, IPA:hexane=7.5:100→3:40), (Fuji Silysia FL-60D 1600 g, IPA:hexane=3:40)
  7. additionFractions containing substantially no impurities
  8. customwere collected
  9. customevaporated

Sources & evidence

ORD record
ord-ea4aee9c6529416a8824d2e6ea772bdb
Source dataset
uspto-grants-2008_04
Patent number
US07355064B2

Reaction notes

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