Sodium Chloride → HCID 24875829, compound

HRID 1874116Notes

Reaction equation

HRID 1874116 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]heptanate (19) (70.49 g, 124.8 mmol) in acetonitrile (705 ml), water (70.5 ml) and 85% phosphoric acid (70.5 ml) were added and the mixture was stirred for 3 hours at approximately 20° C. The solution was supplemented with 10% aqueous sodium chloride (705 ml), and extracted three times with ethyl acetate (276 ml). The organic layers were combined and sequentially washed with 10% aqueous sodium chloride (360 ml), saturated sodium bicarbonate water (360 ml) and saturated aqueous sodium chloride (360 ml). The solution was 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). The fractions containing impurities were re-purified 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-oxooctahydro cyclopenta[b]pyran-5-yl]heptanate (20) (52.64 g; 109.5 mmol; yield: 87.8%) as a colorless oil.

Workup

  1. extractionextracted three times with ethyl acetate (276 ml)
  2. washsequentially washed with 10% aqueous sodium chloride (360 ml), saturated sodium bicarbonate water (360 ml) and saturated aqueous sodium chloride (360 ml)
  3. dry with materialThe solution was dried 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. additionThe fractions containing impurities
  7. customwere re-purified by silica gel column chromatography (Fuji Silysia BW-300 1000 g, ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-ca523bf8eb2d4e30b0117617eb6eb9ae
Source dataset
uspto-grants-2012_11
Patent number
US08304562B2

Reaction notes

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