Ethyl Acetate → HCID 57857073, compound

HRID 561733Notes

Reaction equation

HRID 561733 reaction equation
[F:1][C:2]([F:29])([CH2:21][O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][C@@H:5]1[C@@H:12]2[C@@H:8]([O:9][C:10](=[O:13])[CH2:11]2)[CH2:7][C@H:6]1[O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1.CC(C[AlH]CC(C)C)C.C(OCC)(=O)C>C1COCC1>[F:29][C:2]([F:1])([CH2:21][O:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:3][CH2:4][C@@H:5]1[C@@H:12]2[C@@H:8]([O:9][CH:10]([OH:13])[CH2:11]2)[CH2:7][C@H:6]1[O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydrideHCID 57857065HCID 57857065, compound

Product 1

HCID 57857073HCID 57857073, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(3aR,4R,5R,6aS)-4-(3,3-Difluoro-4-phenoxybutyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one, prepared in Step E, was dissolved in anhydrous THF (0.5 M) under nitrogen atmosphere and cooled to −78° C. A solution consisting of DIBAL-H (2 molar equivalents, 1 M in toluene) is added to the reaction mixture dropwise and stirred for 3 hours. Ethyl acetate (20 mL) is added and the mixture is stirred for an additional 5 minutes. The mixture is subsequently treated with 30% aqueous K, Na tartrate and stirred vigorously overnight. The layers are separated and the organic phase is filtered and concentrated under reduced pressure. The crude product is purified by flash chromatography on regular silica gel eluted with ethyl acetate-hexanes to afford the title intermediate.

Workup

  1. additionis added to the reaction mixture dropwise
  2. stirringthe mixture is stirred for an additional 5 minutes
  3. stirringstirred vigorously overnight
  4. customThe layers are separated
  5. filtrationthe organic phase is filtered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product is purified by flash chromatography on regular silica gel
  8. washeluted with ethyl acetate-hexanes

Sources & evidence

ORD record
ord-61ab568abd8c49619dc9630eadff8512
Source dataset
uspto-grants-2011_11
Patent number
US08063240B2

Reaction notes

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