Benzoyl chloride → (6Z,8aR,9R,10R,11aS)-4,5,8,8a,9,10,11,11a-octahydro-9-((S,E)-5-phenyl-3-(tetra hydro-2H-pyran-2-yloxy)pent-1-enyl)-10-(tetrahydro-2H-pyran-2-yloxy)cyclopenta[b]oxecin-2(3H)-one

HRID 517403Notes

Reaction equation

HRID 517403 reaction equation
O[C@@H:2]1[C@H:6]([CH2:7][CH:8]=[CH:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])[C@@H:5](/[CH:16]=[CH:17]/[C@@H:18]([O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)[CH2:19]CC2C=CC=CC=2)[C@H:4]([O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH2:3]1.C(N(CC)C(C)C)(C)C.[C:50](Cl)(=O)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>ClCCl.CN(C)C1C=CN=CC=1>[C:51]1([CH2:50][CH2:19][C@H:18]([O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)/[CH:17]=[CH:16]/[C@@H:5]2[C@@H:6]3[C@@H:2]([O:14][C:13](=[O:15])[CH2:12][CH2:11][CH2:10][CH:9]=[CH:8][CH2:7]3)[CH2:3][C@H:4]2[O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

6

Reactant 3

HCID 7412Benzoyl chlorideHCID 81531DiisopropylethylamineHCID 1317333507-((1R,2R,3R,5S)-5-hydroxy-2-((S,E)-5-phenyl-3-(tetrahydro-2H-pyran-2-yloxy) pent-1-enyl)-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)hept-5-enoic acid

Product 1

HCID 117875096(6Z,8aR,9R,10R,11aS)-4,5,8,8a,9,10,11,11a-octahydro-9-((S,E)-5-phenyl-3-(tetra hydro-2H-pyran-2-yloxy)pent-1-enyl)-10-(tetrahydro-2H-pyran-2-yloxy)cyclopenta[b]oxecin-2(3H)-oneYield 58.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 7-((1R,2R,3R,5S)-5-hydroxy-2-((S,E)-5-phenyl-3-(tetrahydro-2H-pyran-2-yloxy)pent-1-enyl)-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)hept-5-enoic acid (32 g from example 48) in 320 mL dichloromethane was treated with N,N-diisopropyl-ethylamine (12.3 g, 94.8 mmol) and benzoyl chloride (7.9 g, 56.3 mmol. This mixture was then stirred for 10 minutes at room temperature under an atmosphere of nitrogen, followed by addition of 4-(dimethylamino)-pyridine (11.9 g, 97.7 mmol) at 0° C. while stirring for 10 minutes. The resulting mixture was quenched with a saturated sodium bicarbonate solution (300 mL) and extracted with dichloromethane (100 mL). The organic layer is dried over magnesium sulfate and concentrated under reduced pressure to give 29.0 g of crude product. The crude product was purified by column chromatography providing 9.4 g of the title compound (58.6% yield, 3 steps).

Workup

  1. stirringwhile stirring for 10 minutes
  2. customThe resulting mixture was quenched with a saturated sodium bicarbonate solution (300 mL)
  3. extractionextracted with dichloromethane (100 mL)
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give 29.0 g of crude product
  7. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-02b31171c498488f90e0dbe4e0b50bab
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Reaction notes

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