Benzyl Bromide → HCID 24875734, compound

HRID 883726Notes

Reaction equation

HRID 883726 reaction equation
[F:1][C:2]([F:33])([CH2:29][CH2:30][CH2:31][CH3:32])[CH:3]([OH:28])[CH2:4][CH2:5][C@H:6]1[C@H:10]([O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[CH2:9][C@H:8]([OH:18])[C@@H:7]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26].C(N(C(C)C)CC)(C)C.[CH2:43](Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(#N)C>[F:33][C:2]([F:1])([CH2:29][CH2:30][CH2:31][CH3:32])[CH:3]([OH:28])[CH2:4][CH2:5][C@H:6]1[C@H:10]([O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[CH2:9][C@H:8]([OH:18])[C@@H:7]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:26]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 81531DiisopropylethylamineHCID 59550267HCID 59550267, compound

Product 1

HCID 24875734HCID 24875734, compoundYield 99.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To the crude 7-[(1R,2R,3R,5S)-2-(4,4-difluoro-3-hydroxyoctyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanoic acid (17) (132.1 mmol) in acetonitrile (315 ml), diisopropyl ethylamine (69.0 ml, 369 mmol) and benzyl bromide (47.1 ml, 369 mmol) were added and the mixture was stirred for 14 hours at room temperature. The reaction mixture was concentrated under reduced pressure, ethyl acetate (366 ml) and water (280 ml) were added to the residue and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with ethyl acetate (224 ml). The organic layers were combined and washed with 1N-hydrochloric acid (336 ml), saturated sodium bicarbonate water (336 ml) and saturated aqueous sodium chloride (336 ml). After drying with anhydrous magnesium sulfate (51 g), the solution was concentrated under reduced pressure. The concentration residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2400 g; ethyl acetate:hexane =1:2) to give benzyl 7-[(1R,2R,3R,5S)-2-(4,4-difluoro-3-hydroxyoctyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (18) (74.44 g; 130.9 mmol; yield: 99.1%) as a colorless oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate (366 ml) and water (280 ml)
  2. additionwere added to the residue
  3. stirringthe mixture was stirred
  4. customseparated into two layers
  5. extractionThe aqueous layer was extracted twice with ethyl acetate (224 ml)
  6. washwashed with 1N-hydrochloric acid (336 ml), saturated sodium bicarbonate water (336 ml) and saturated aqueous sodium chloride (336 ml)
  7. dry with materialAfter drying with anhydrous magnesium sulfate (51 g)
  8. concentrationthe solution was concentrated under reduced pressure
  9. customThe concentration residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2400 g; ethyl acetate:hexane =1:2)

Sources & evidence

ORD record
ord-f4d1c62c62f54032932438d3f63004a4
Source dataset
uspto-grants-2012_08
Patent number
US08236969B2

Reaction notes

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