p-Toluenesulfonic acid → (S)alpha-[(2S)(6-bromo-hexahydro-3,5-methano-2H-cyclopenta[b]furan-2-yl)-oxy]-3-phenoxy-benzene-acetonitrile

HRID 256231

Reaction equation

HRID 256231 reaction equation
[Br:1][CH:2]1[CH:6]2[O:7][CH:8]([OH:11])[CH:9]3[CH2:10][CH:3]1[CH2:4][CH:5]23.[C:12]1([CH3:22])[CH:17]=[CH:16][C:15](S(O)(=O)=O)=[CH:14][CH:13]=1.C[N:24]([CH3:27])C=O>C(Cl)Cl>[Br:1][CH:2]1[CH:6]2[O:7][C@H:8]([O:11][C@@H:22]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:7][C:6]4[CH:2]=[CH:3][CH:10]=[CH:9][CH:5]=4)[CH:13]=3)[C:27]#[N:24])[CH:9]3[CH2:10][CH:3]1[CH2:4][CH:5]23

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 6228Dimethylformamide2×HCID 212840296-bromo-hexahydro-3,5-methano-2H-cyclopenta[b]furan-2-ol

Product 1

HCID 70372766(S)alpha-[(2S)(6-bromo-hexahydro-3,5-methano-2H-cyclopenta[b]furan-2-yl)-oxy]-3-phenoxy-benzene-acetonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2.19 g of the product of Step B in 50 ml of methylene chloride was added to a refluxing mixture of 2.93 g of (R,S)α-cyano-3-phenoxy-benzyl alcohol, 100 ml of methylene chloride and 300 mg of p-toluene sulfonic acid and the mixture was refluxed for another 15 minutes and then returned to room temperature. The mixture was washed with water, dried, vacuum filtered and evaporated to dryness under reduced pressure. The 4.34 g of the (R,S)α-[(2S)(6-bromo-hexahydro-3,5-methano-2H-cyclopenta[b]furan-2-yl)-oxy]-3-phenoxy-benzene acetonitrile were chromatographed over silica gel and eluted with a 9-1 hexane-ethyl acetate mixture to obtain the (S)α-isomer melting at 65° C. and having a specific rotation of [α]D20 =+110° (c=0.5% in dimethylformamide) and the (R)α-isomer with a specific rotation of [α]D20 =+108.5° (c=0.4% in dimethylformamide).

Workup

  1. temperaturethe mixture was refluxed for another 15 minutes
  2. customreturned to room temperature
  3. washThe mixture was washed with water
  4. customdried
  5. filtrationvacuum filtered
  6. customevaporated to dryness under reduced pressure
  7. customThe 4.34 g of the (R,S)α-[(2S)(6-bromo-hexahydro-3,5-methano-2H-cyclopenta[b]furan-2-yl)-oxy]-3-phenoxy-benzene acetonitrile were chromatographed over silica gel
  8. washeluted with a 9-1 hexane-ethyl acetate mixture
  9. customto obtain the (S)α-isomer melting at 65° C.

Sources & evidence

ORD record
ord-89580c9318d1433dae774e68bc085dd8
Source dataset
uspto-grants-1987_10
Patent number
US04701542

Linked notes

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